Puretech announces annual results for year ended december 31, 2020
Boston--(business wire)--puretech health plc (nasdaq: prtc, lse: prtc) ("puretech" or the "company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, today announced its results for the year ended december 31, 2020 as well as its cash balance as of the first quarter ended march 31, 2021. the following information represents select highlights from the full report, which will be filed as an exhibit to form 20-f with the united states securities and exchange commission and is also available at https://investors.puretechhealth.com/financials-filings/reports. webcast and conference call details members of the puretech management team will host a conference call at 9:00am edt / 2:00pm bst today, april 15, to discuss these results. a live webcast and presentation slides will be available on the investors section of puretech’s website under the events and presentations tab. to join by phone, please dial: united kingdom: 0800 640 6441 united kingdom (local): 020 3936 2999 united states: 1 855 9796 654 united states (local): 1 646 664 1960 all other locations: +44 20 3936 2999 access code: 440629 for those unable to listen to the call live, a replay will be available on the puretech website. commenting on the annual results, daphne zohar, founder and chief executive officer of puretech said: “2020 was a year like no other. for our team at puretech, it was defined both by transformational progress and tremendous resilience, as we realized significant financial, clinical and regulatory milestones while navigating the challenges of a global pandemic. i am immensely proud of our team’s dedication to our mission: develop groundbreaking medicines for serious diseases for which patients currently have few options. “we now have 26 therapeutics and therapeutic candidates being advanced through our wholly owned pipeline or our founded entities. this includes two therapeutics that have received fda clearance and european marketing authorization - gelesis’ plenity® and akili’s endeavorrxtm – both of which were initially conceived of and advanced by the puretech team to address urgent medical needs for patients. we expect a broader u.s. launch for both therapeutics this year. “we made notable progress in the advancement of our wholly owned pipeline this year, initiating four clinical trials and reporting the successful completion of one clinical trial. we are currently evaluating two candidates – lyt-100 and lyt-200 – across three different indications where there is serious need. i am also pleased to have expanded our wholly owned pipeline with the nomination of a new therapeutic candidate, lyt-300 (oral allopregnanolone), which we expect to enter a clinical trial by the end of 2021. “additionally, we continued to solidify our financial position by generating $350.6 million in 2020 and an additional $118 million in the february 2021 post-period via the monetization of partial stakes in founded entities. we also successfully completed a listing of american depository shares on the nasdaq global market in november 2020, which enables us to broaden access to an international investor base as we maintained our premium listing on the london stock exchange and our membership in the ftse 250. “we are well-positioned for an exciting year ahead, which we expect will include multiple value drivers across our wholly owned programs and our founded entities, including at least ten expected clinical trial initiations and nine expected readouts. “i would like to thank our shareholders for their vision and continued support over the last year. above all, i would like to thank the patients and clinicians working alongside us in our clinical trials. we are grateful for your support, humbled by your trust and inspired by your courage. you make possible the medical advances of the future.” continued advancement and growth of wholly owned programs7 our team, network and expertise in the big axis has enabled the rapid advancement and growth of our wholly owned programs. focused on the lymphatic system and related immunological disorders, our wholly owned pipeline currently consists of lyt-100, a clinical-stage therapeutic candidate we are pursuing for inflammatory and fibrotic conditions and disorders of lymphatic flow, lyt-200, a clinical therapeutic candidate targeting a foundational immunosuppressive protein, galectin-9, we are developing for the potential treatment of a range of cancer indications, lyt-210, a preclinical therapeutic candidate targeting immunomodulatory gamma delta-1 t cells we are developing for a range of cancer indications and autoimmune disorders and lyt-300, a preclinical therapeutic candidate we are developing for a range of neurological and neuropsychological conditions. our wholly owned programs also include three discovery platforms: glyph™ – our synthetic lymphatic targeting chemistry platform – and orasome™ – our oral biotherapeutics platform – both of which leverage absorption of dietary lipids to traffic therapeutics via the lymphatic system, and our meningeal lymphatics discovery research program for treating neurodegenerative and neuroinflammatory diseases. key developments included the following: program highlights lyt-100 in november 2020, we announced the completion of a phase 1 randomized, double-blind multiple ascending dose and food effect study of lyt-100, which was initiated in march 2020. the study demonstrated favorable proof-of-concept for lyt-100’s tolerability and pharmacokinetic, or pk, profile. in december 2020, we announced the initiation of a global, randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy, safety and tolerability of lyt-100 in adults with long covid respiratory complications and related sequelae. topline results are expected in the second half of 2021. in december 2020, we announced the initiation of a phase 2a proof-of-concept study of lyt-100 in patients with breast cancer-related, upper limb secondary lymphedema. topline results are expected in the first half of 2022. we are planning registration-enabling studies of lyt-100 for the treatment of idiopathic pulmonary fibrosis, or ipf, and potentially other progressive fibrosing interstitial lung diseases, or pf-ilds, and we expect to provide additional guidance later this year. lyt-200 in december 2020, we announced the initiation of our phase 1 clinical trial to evaluate lyt-200 as a potential treatment for metastatic solid tumors, with topline results anticipated in the fourth quarter of 2021. the primary objective of the phase 1 portion of the adaptive phase 1/2 trial is to assess the safety and tolerability of escalating doses of lyt-200 in order to identify a dose to carry forward into the phase 2 portion of the trial. the phase 1 portion will also assess the pk and pharmacodynamic, or pd, profiles of lyt-200. pending favorable topline results, we intend to initiate the phase 2 expansion cohort portion of the trial, which is designed to evaluate lyt-200 either alone and/or in combination with chemotherapy and anti-pd-1 therapy for the treatment of multiple solid tumor types, including pancreatic cancer and cholangiocarcinoma, or cca. in june 2020, we presented a scientific poster for lyt-200 at the american association for cancer research, or aacr, 2020 virtual annual meeting. new preclinical results were presented that established galectin-9 as a novel target for cancer immunotherapy. lyt-300 and the glyph™ technology platform we are advancing our glyph technology platform, which is designed to employ the body’s natural lipid absorption and transport process to orally administer drugs via the lymphatic system. we have successfully extended the platform to encompass more than 20 molecules as well as a range of novel linker chemistries that have demonstrated promising lymphatic targeting in preclinical studies. our most advanced glyph candidate, lyt-300, is an oral form of allopregnanolone, an fda-approved drug, which is a natural neurosteroid that we believe may be applicable to a range of neurological conditions. we expect to initiate a clinical trial with lyt-300 by the end of 2021. in the february 2021 post-period, preclinical proof-of-concept for our glyph technology was published in the journal of controlled release. the results demonstrate the ability of this platform to directly target gut lymphatics with an orally dosed small molecule immunomodulator. orasome™ technology platform we progressed our orasome technology platform, which utilizes multiple vesicle components, including those isolated from milk. our orasome vesicles are being designed to transport macromolecular medicines to selected mucosal cell types of the intestinal tract. in 2021, we expect preclinical proof-of-concept data and anticipate additional preclinical results from a non-human primate proof-of-concept study. this work could lay the foundation for investigational new drug, or ind, application enabling clinical studies for one or more additional therapeutic candidates to be included in our wholly owned pipeline. corporate highlights on november 16, 2020, we commenced trading of american depository shares, or adss, on the nasdaq global market under the ticker symbol “prtc” (the “u.s. listing”). in addition to the u.s. listing, we maintain our premium listing on the official list of the uk financial conduct authority and trading on the main market of the london stock exchange. our ticker symbol in the uk is also prtc, and we are a member of the ftse250 index. in october 2020, we announced the appointment of biotech entrepreneur kiran mazumdar-shaw to our board of directors. ms. shaw brings extensive experience in biotherapeutics, strategic leadership, financial and business development and a dedication to improving patients’ lives to our board of industry leaders. in the january 2021 post-period, we announced that george farmer, ph.d., was appointed as chief financial officer. dr. farmer is responsible for all aspects of our finances, including capital markets strategy and execution, strategic and financial planning and financial reporting. financial highlights in 2020, we sold shares in our founded entities for cash consideration of $350.6 million, while in the february 2021 post-period we sold an additional one million shares in karuna therapeutics, inc. for cash consideration of $118 million. puretech level cash and cash equivalents were $443.4 million as of march 31, 20211 and $349.4 million as of december 31, 20202. we extended our cash runway guidance by one year into the first quarter of 2025. consolidated cash and cash equivalents, which includes cash held at the puretech level and at controlled founded entities, were $486.5 million as of march 31, 20213 and $403.9 million as of december 31, 20204. puretech’s founded entities raised $247.8 million in 20205 and an additional $473.2 million in the 2021 post-period6, almost all of which came from third parties. significant regulatory, clinical and financial momentum across puretech’s founded entities8 puretech’s founded entities have made significant progress advancing 22 therapeutics and therapeutic candidates, of which two have been cleared for marketing by the u.s. food and drug administration and granted marketing authorization in the european economic area and 13 are clinical stage. key developments included the following: founded entities in which puretech has a controlling interest or the right to receive royalties, in order of development stage: gelesis, inc. (puretech ownership: 19.3%; we also have a right to royalty payments as a percentage of net sales) in june 2020, gelesis received approval to market plenity®9 with a conformitÉ europÉenne, or ce, mark as a class iii medical device indicated for weight loss in overweight and obese adults with a body mass index, or bmi, of 25-40 kg/m2, when used in conjunction with diet and exercise. in addition to its u.s. fda clearance, gelesis is now able to market plenity® throughout the european economic area and in other countries that recognize the ce mark. gelesis plans to bring plenity to the u.s. first, where it has been available to a limited extent since the second half of 2019 through an early experience program and since 2020 via a beta launch while the company ramps up its commercial operations and inventory for a broader launch in the second half of 2021. in just one month of limited promotion and marketing investment during the limited launch, gelesis acquired more new patients on plenity, than any other branded prescription in the weight loss market. gelesis also plans to seek fda input on the requirements for expanding the plenity label for treating adolescents. in june 2020, gelesis announced a partnership with china medical system holdings ltd., or cms, for the commercialization of plenity in china. through the terms of the deal, cms provided $35 million upfront in a combination of licensing fees and equity investment, with the potential for an additional $388 million in future milestone payments as well as royalties. in the second half of 2020, gelesis initiated a phase 3 study of gs500 in functional constipation. in november 2020, gelesis’ collaborator alessandra silvestri, ph.d., of the laboratory of mucosal immunology and microbiota at humanitas research hospital, presented a poster on the therapeutic benefits of gel-b (gs300) at the liver meeting, the american association for the study of liver diseases, or aasld, annual conference. the data demonstrated that, in a preclinical model, the proprietary therapeutic candidate reversed the damage to the intestines induced by a high fat diet and gelesis believes that therapies exploiting the gut liver axis may offer a unique treatment option for metabolic liver disorders. also in november 2020, gelesis presented three posters at obesityweek 2020, the annual congress of the obesity society. presentations included new data that showed that prediabetes and impaired beta cell function were associated with a dysfunctional gut barrier, a potential precursor to metabolic diseases; an additional analysis of gelesis’ pivotal glow study suggested fasting plasma glucose levels and insulin resistance could be strong predictors of weight loss with plenity; and a new in vitro beverage interaction study that demonstrated plenity’s hydrogel maintained its properties in the presence of alcoholic or acidic drinks. in september 2020, gelesis delivered one oral presentation and two poster presentations showcasing notable efficacy data for plenity® at the european and international congress on obesity, or eco-ico 2020. in march 2020, gelesis was named to fast company’s list of the world’s most innovative companies for 2020. in june 2020, gelesis received approval to market plenity®9 with a conformitÉ europÉenne, or ce, mark as a class iii medical device indicated for weight loss in overweight and obese adults with a body mass index, or bmi, of 25-40 kg/m2, when used in conjunction with diet and exercise. in addition to its u.s. fda clearance, gelesis is now able to market plenity® throughout the european economic area and in other countries that recognize the ce mark. gelesis plans to bring plenity to the u.s. first, where it has been available to a limited extent since the second half of 2019 through an early experience program and since 2020 via a beta launch while the company ramps up its commercial operations and inventory for a broader launch in the second half of 2021. in just one month of limited promotion and marketing investment during the limited launch, gelesis acquired more new patients on plenity, than any other branded prescription in the weight loss market. gelesis also plans to seek fda input on the requirements for expanding the plenity label for treating adolescents. in june 2020, gelesis announced a partnership with china medical system holdings ltd., or cms, for the commercialization of plenity in china. through the terms of the deal, cms provided $35 million upfront in a combination of licensing fees and equity investment, with the potential for an additional $388 million in future milestone payments as well as royalties. in the second half of 2020, gelesis initiated a phase 3 study of gs500 in functional constipation. in november 2020, gelesis’ collaborator alessandra silvestri, ph.d., of the laboratory of mucosal immunology and microbiota at humanitas research hospital, presented a poster on the therapeutic benefits of gel-b (gs300) at the liver meeting, the american association for the study of liver diseases, or aasld, annual conference. the data demonstrated that, in a preclinical model, the proprietary therapeutic candidate reversed the damage to the intestines induced by a high fat diet and gelesis believes that therapies exploiting the gut liver axis may offer a unique treatment option for metabolic liver disorders. also in november 2020, gelesis presented three posters at obesityweek 2020, the annual congress of the obesity society. presentations included new data that showed that prediabetes and impaired beta cell function were associated with a dysfunctional gut barrier, a potential precursor to metabolic diseases; an additional analysis of gelesis’ pivotal glow study suggested fasting plasma glucose levels and insulin resistance could be strong predictors of weight loss with plenity; and a new in vitro beverage interaction study that demonstrated plenity’s hydrogel maintained its properties in the presence of alcoholic or acidic drinks. in september 2020, gelesis delivered one oral presentation and two poster presentations showcasing notable efficacy data for plenity® at the european and international congress on obesity, or eco-ico 2020. in march 2020, gelesis was named to fast company’s list of the world’s most innovative companies for 2020. karuna therapeutics, inc. (puretech ownership: 8.2%; we also have a right to royalty payments as a percentage of net sales) in june 2020, karuna announced next steps in the emergent program, the clinical program evaluating karxt for the treatment of adults with schizophrenia, following the completion of a successful end-of-phase 2 meeting with the fda. in december 2020, karuna announced the initiation of the phase 3 emergent-2 trial, the first of two phase 3 five-week inpatient trials evaluating the efficacy and safety of karxt for the treatment of acute psychosis in adults with schizophrenia. in may 2020, karuna presented data from emergent-1, the phase 2 clinical trial evaluating karxt for the treatment of acute psychosis in patients with schizophrenia, at the american society of clinical psychopharmacology, or ascp, 2020 annual meeting. the poster and oral presentation detailed new and previously reported efficacy and safety data from the phase 2 clinical trial. in the first quarter of the 2021 post-period, karuna announced the initiation of the phase 3 emergent-4 trial, a 52-week, outpatient, open-label long-term safety and tolerability extension trial of emergent-2 and emergent-3. in the february 2021 post-period, karuna announced that results from the emergent-1 phase 2 clinical trial evaluating karxt for the treatment of schizophrenia were published in the new england journal of medicine, or nejm. in june 2020, karuna announced next steps in the emergent program, the clinical program evaluating karxt for the treatment of adults with schizophrenia, following the completion of a successful end-of-phase 2 meeting with the fda. in december 2020, karuna announced the initiation of the phase 3 emergent-2 trial, the first of two phase 3 five-week inpatient trials evaluating the efficacy and safety of karxt for the treatment of acute psychosis in adults with schizophrenia. in may 2020, karuna presented data from emergent-1, the phase 2 clinical trial evaluating karxt for the treatment of acute psychosis in patients with schizophrenia, at the american society of clinical psychopharmacology, or ascp, 2020 annual meeting. the poster and oral presentation detailed new and previously reported efficacy and safety data from the phase 2 clinical trial. in the first quarter of the 2021 post-period, karuna announced the initiation of the phase 3 emergent-4 trial, a 52-week, outpatient, open-label long-term safety and tolerability extension trial of emergent-2 and emergent-3. in the february 2021 post-period, karuna announced that results from the emergent-1 phase 2 clinical trial evaluating karxt for the treatment of schizophrenia were published in the new england journal of medicine, or nejm. follica, incorporated (puretech ownership: 78.2%; we also have a right to royalty payments as a percentage of net sales) in june 2020, follica announced the completion of a successful end-of-phase 2 meeting with the fda for its lead program to treat male androgenetic alopecia, which supports the progression into phase 3 development. the initiation of a phase 3 registration program in male androgenetic alopecia is expected in 2021. in december 2020, follica announced the publication of a pilot study evaluating scalp skin disruption to promote hair growth in female pattern hair loss, or fphl, in international journal of women’s dermatology. the pilot study, led by maryanne m. senna, m.d., an assistant professor of dermatology at harvard medical school, demonstrated the treatment promoted hair growth over a four-month course of treatment. in the january 2021 post-period, follica announced the appointment of two leaders in aesthetic medicine and dermatology to its board of directors. tom wiggans, former ceo of dermira, joined as executive chairman with over 30 years of experience leading biopharmaceutical companies from the start-up stage to global commercialization, and michael davin, former ceo of cynosure, joined as an independent director with over 30 years of experience in the medical device industry. in june 2020, follica announced the completion of a successful end-of-phase 2 meeting with the fda for its lead program to treat male androgenetic alopecia, which supports the progression into phase 3 development. the initiation of a phase 3 registration program in male androgenetic alopecia is expected in 2021. in december 2020, follica announced the publication of a pilot study evaluating scalp skin disruption to promote hair growth in female pattern hair loss, or fphl, in international journal of women’s dermatology. the pilot study, led by maryanne m. senna, m.d., an assistant professor of dermatology at harvard medical school, demonstrated the treatment promoted hair growth over a four-month course of treatment. in the january 2021 post-period, follica announced the appointment of two leaders in aesthetic medicine and dermatology to its board of directors. tom wiggans, former ceo of dermira, joined as executive chairman with over 30 years of experience leading biopharmaceutical companies from the start-up stage to global commercialization, and michael davin, former ceo of cynosure, joined as an independent director with over 30 years of experience in the medical device industry. vedanta biosciences, inc. (puretech ownership: 49.5%) in june 2020, vedanta announced topline phase 1 clinical data in healthy volunteers, which showed that ve202, vedanta’s orally-administered live biotherapeutic product, or lbp, candidate for inflammatory bowel disease, or ibd, was generally well-tolerated at all doses studied and demonstrated durable and dose-dependent colonization. the trial was conducted by janssen research & development, llc, and a more complete study dataset and analyses will be submitted to a peer-reviewed journal. vedanta expects to advance ve202 into a phase 2 study for ibd in 2021. vedanta has regained full rights to the program and will owe janssen single-digit royalty payments on net sales of a commercialized product. in the january 2021 post-period, vedanta announced a $25 million investment from pfizer as part of the pfizer breakthrough growth initiative. the proceeds will fund the phase 2 study of ve202 in ibd. vedanta will retain control of all its programs and has granted pfizer a right of first negotiation on ve202. in october 2020, additional data from a phase 1 clinical study of ve202 in healthy volunteers was presented by janssen research & development, llc, at united european gastroenterology, or ueg, week 2020. the new ueg week data presentation focused on the kinetics and durability of colonization from an 11-strain consortium of ve202 under various dosing and pre-treatment regimens. vedanta has also continued to progress its three ongoing clinical trials of ve303, ve416 and ve800. in 2021, vedanta anticipates topline results from a phase 2 trial of ve303 in high-risk clostridioides difficile infection, or cdi and a first-in-patient clinical trial of ve800 in combination with bristol- myers squibb’s checkpoint inhibitor opdivo® (nivolumab) in patients with select types of advanced or metastatic cancer. topline results from a phase 1/2 trial of ve416 for food allergy are expected in 2022. in june 2020, vedanta strengthened its balance sheet with an additional $12 million in new equity and r&d collaboration funds, bringing its total series c round to $71.1 million. in september 2020, vedanta announced it has been awarded funding of $7.4 million, with the potential for up to an additional $69.5 million, from the biomedical advanced research and development authority, or barda, to advance clinical development of ve303 for high-risk cdi. vedanta is the first-ever recipient of a barda award in the microbiome field. in june 2020, vedanta announced topline phase 1 clinical data in healthy volunteers, which showed that ve202, vedanta’s orally-administered live biotherapeutic product, or lbp, candidate for inflammatory bowel disease, or ibd, was generally well-tolerated at all doses studied and demonstrated durable and dose-dependent colonization. the trial was conducted by janssen research & development, llc, and a more complete study dataset and analyses will be submitted to a peer-reviewed journal. vedanta expects to advance ve202 into a phase 2 study for ibd in 2021. vedanta has regained full rights to the program and will owe janssen single-digit royalty payments on net sales of a commercialized product. in the january 2021 post-period, vedanta announced a $25 million investment from pfizer as part of the pfizer breakthrough growth initiative. the proceeds will fund the phase 2 study of ve202 in ibd. vedanta will retain control of all its programs and has granted pfizer a right of first negotiation on ve202. in october 2020, additional data from a phase 1 clinical study of ve202 in healthy volunteers was presented by janssen research & development, llc, at united european gastroenterology, or ueg, week 2020. the new ueg week data presentation focused on the kinetics and durability of colonization from an 11-strain consortium of ve202 under various dosing and pre-treatment regimens. vedanta has also continued to progress its three ongoing clinical trials of ve303, ve416 and ve800. in 2021, vedanta anticipates topline results from a phase 2 trial of ve303 in high-risk clostridioides difficile infection, or cdi and a first-in-patient clinical trial of ve800 in combination with bristol- myers squibb’s checkpoint inhibitor opdivo® (nivolumab) in patients with select types of advanced or metastatic cancer. topline results from a phase 1/2 trial of ve416 for food allergy are expected in 2022. in june 2020, vedanta strengthened its balance sheet with an additional $12 million in new equity and r&d collaboration funds, bringing its total series c round to $71.1 million. in september 2020, vedanta announced it has been awarded funding of $7.4 million, with the potential for up to an additional $69.5 million, from the biomedical advanced research and development authority, or barda, to advance clinical development of ve303 for high-risk cdi. vedanta is the first-ever recipient of a barda award in the microbiome field. sonde health, inc. (puretech ownership: 44.6%) in july 2020, sonde launched sonde one for respiratory, a new voice-enabled health detection and monitoring app, to potentially help employers improve employee safety, meet government mandates and satisfy their own administrative needs as they reopen office doors in a covid-19 environment. in august 2020, sonde acquired neurolex labs, a leading voice-enabled survey and data acquisition platform. the transaction did not involve any financial participation from puretech. in november 2020, sonde announced the launch of a new developer portal that provides organizations with access to sonde’s advanced vocal biomarker-based health check technology. as part of the launch, sonde has introduced a new self-serve application programming interface, or api, and documentation to allow developers to quickly, easily, and autonomously integrate sonde’s voice-enabled respiratory symptoms checker into their own ios and android mobile applications. sonde has collected over one million voice samples from over 80,000 subjects as a part of the ongoing validation of its platform, and it has also initiated research and development to expand its proprietary technology into alzheimer’s disease, or ad, respiratory and cardiovascular disease, as well as other health and wellness conditions, including mental health. in july 2020, sonde launched sonde one for respiratory, a new voice-enabled health detection and monitoring app, to potentially help employers improve employee safety, meet government mandates and satisfy their own administrative needs as they reopen office doors in a covid-19 environment. in august 2020, sonde acquired neurolex labs, a leading voice-enabled survey and data acquisition platform. the transaction did not involve any financial participation from puretech. in november 2020, sonde announced the launch of a new developer portal that provides organizations with access to sonde’s advanced vocal biomarker-based health check technology. as part of the launch, sonde has introduced a new self-serve application programming interface, or api, and documentation to allow developers to quickly, easily, and autonomously integrate sonde’s voice-enabled respiratory symptoms checker into their own ios and android mobile applications. sonde has collected over one million voice samples from over 80,000 subjects as a part of the ongoing validation of its platform, and it has also initiated research and development to expand its proprietary technology into alzheimer’s disease, or ad, respiratory and cardiovascular disease, as well as other health and wellness conditions, including mental health. alivio therapeutics, inc. (puretech ownership: 78.0%) alivio continued to advance its targeted disease immunomodulation platform for the potential treatment of chronic and acute inflammatory disorders. alivio expects an ind filing for alv-107 for interstitial cystitis or bladder pain syndrome, or ic/bps, in 2021 and an ind for alv-304 in ibd in 2023. alivio is also evaluating the potential application of its proprietary platform to enable the oral administration of biologics in additional indications. in october 2020, alivio announced a $3.3 million u.s. department of defense, or dod, technology/therapeutic development award to advance its therapeutic candidate, alv-304, for the treatment of ibd. the funds will support alivio’s preclinical research and development activities to potentially enable the ind filing. alivio continued to advance its targeted disease immunomodulation platform for the potential treatment of chronic and acute inflammatory disorders. alivio expects an ind filing for alv-107 for interstitial cystitis or bladder pain syndrome, or ic/bps, in 2021 and an ind for alv-304 in ibd in 2023. alivio is also evaluating the potential application of its proprietary platform to enable the oral administration of biologics in additional indications. in october 2020, alivio announced a $3.3 million u.s. department of defense, or dod, technology/therapeutic development award to advance its therapeutic candidate, alv-304, for the treatment of ibd. the funds will support alivio’s preclinical research and development activities to potentially enable the ind filing. entrega, inc. (puretech ownership: 72.9%) entrega continued to advance its platform for the oral administration of biologics, vaccines and other drugs that are otherwise not efficiently absorbed when taken orally. as part of its collaboration with eli lilly, entrega has continued to investigate the application of its peptide administration technology to certain lilly therapeutic candidates. in 2020, the partnership was extended into 2021. entrega continued to advance its platform for the oral administration of biologics, vaccines and other drugs that are otherwise not efficiently absorbed when taken orally. as part of its collaboration with eli lilly, entrega has continued to investigate the application of its peptide administration technology to certain lilly therapeutic candidates. in 2020, the partnership was extended into 2021. founded entities in which puretech has an equity interest, in order of development stage: akili interactive labs, inc. (puretech ownership: 33.7%) in june 2020, akili received clearance from the fda to market endeavorrx™10 (akl-t01) as a prescription treatment for improving attention function in children with attention-deficit/hyperactivity disorder, or adhd. delivered through a captivating video game experience, endeavorrx is indicated to improve attention function as measured by computer-based testing in children ages 8-12 years old with primarily inattentive or combined-type adhd, who have a demonstrated attention issue. akili plans to take a scaled approach to the commercial launch of endeavorrx in 2021. the fda clearance followed the april 2020 announcement that endeavor™ would be available for use for a limited time by children with adhd and their families in response to new guidance from the fda recognizing the need for access to certain low-risk clinically-validated digital health devices for psychiatric conditions, including adhd, during the covid-19 pandemic. also in june 2020, akili announced that it had received approval to market endeavorrx in europe. akili received a ce mark certification for endeavorrx as a prescription-only digital therapeutic intended for the treatment of attention and inhibitory control deficits in pediatric patients with adhd. the ce mark approval enables the future marketing of endeavorrx in european economic area member countries. with a near-term focus on launching the endeavorrx prescription treatment in the u.s. first, akili is exploring expansion opportunities in europe as part of its global strategy. in the april 2021 post-period, akili announced collaborations with weill cornell medicine, newyork-presbyterian hospital and vanderbilt university medical center to evaluate akili digital therapeutic akl-t01 as a treatment for patients with cognitive dysfunction following covid-19 (also known as “covid brain fog”). under each collaboration, akili will work with research teams at each institution to conduct two separate randomized, controlled clinical studies evaluating akl-t01’s ability to target and improve cognitive functioning in covid-19 survivors who have exhibited a deficit in cognition. in january 2020, akili announced that its stars adjunct trial achieved its primary endpoint evaluating the effects of endeavorrx in children with adhd when used with and without stimulant medication. the study achieved its predefined primary efficacy outcome, demonstrating a statistically significant improvement in the adhd impairment rating scale, or irs, from baseline after one month of treatment (p<0.001) in both children taking stimulant medications and in those not taking stimulants. in february 2020, the lancet digital health journal published the results from akili’s stars-adhd pivotal trial of akl-t01. in october 2020, akili announced multiple data presentations on endeavorrx, including results from the stars adjunct trial, a multi-site open-label study designed to evaluate the impact of endeavorrx on impairments in daily life in children with adhd and inform prescribing practices. also presented were analyses across four clinical trials of endeavorrx, evaluating the impact of treatment on children’s attention function compared to normative ranges. the data were presented for the first time at the american academy of child and adolescent psychiatry, or aacap, 2020 virtual annual meeting. in the march 2021 post-period, nature digital medicine published the full results from the stars adjunct trial. in june 2020, akili received clearance from the fda to market endeavorrx™10 (akl-t01) as a prescription treatment for improving attention function in children with attention-deficit/hyperactivity disorder, or adhd. delivered through a captivating video game experience, endeavorrx is indicated to improve attention function as measured by computer-based testing in children ages 8-12 years old with primarily inattentive or combined-type adhd, who have a demonstrated attention issue. akili plans to take a scaled approach to the commercial launch of endeavorrx in 2021. the fda clearance followed the april 2020 announcement that endeavor™ would be available for use for a limited time by children with adhd and their families in response to new guidance from the fda recognizing the need for access to certain low-risk clinically-validated digital health devices for psychiatric conditions, including adhd, during the covid-19 pandemic. also in june 2020, akili announced that it had received approval to market endeavorrx in europe. akili received a ce mark certification for endeavorrx as a prescription-only digital therapeutic intended for the treatment of attention and inhibitory control deficits in pediatric patients with adhd. the ce mark approval enables the future marketing of endeavorrx in european economic area member countries. with a near-term focus on launching the endeavorrx prescription treatment in the u.s. first, akili is exploring expansion opportunities in europe as part of its global strategy. in the april 2021 post-period, akili announced collaborations with weill cornell medicine, newyork-presbyterian hospital and vanderbilt university medical center to evaluate akili digital therapeutic akl-t01 as a treatment for patients with cognitive dysfunction following covid-19 (also known as “covid brain fog”). under each collaboration, akili will work with research teams at each institution to conduct two separate randomized, controlled clinical studies evaluating akl-t01’s ability to target and improve cognitive functioning in covid-19 survivors who have exhibited a deficit in cognition. in january 2020, akili announced that its stars adjunct trial achieved its primary endpoint evaluating the effects of endeavorrx in children with adhd when used with and without stimulant medication. the study achieved its predefined primary efficacy outcome, demonstrating a statistically significant improvement in the adhd impairment rating scale, or irs, from baseline after one month of treatment (p<0.001) in both children taking stimulant medications and in those not taking stimulants. in february 2020, the lancet digital health journal published the results from akili’s stars-adhd pivotal trial of akl-t01. in october 2020, akili announced multiple data presentations on endeavorrx, including results from the stars adjunct trial, a multi-site open-label study designed to evaluate the impact of endeavorrx on impairments in daily life in children with adhd and inform prescribing practices. also presented were analyses across four clinical trials of endeavorrx, evaluating the impact of treatment on children’s attention function compared to normative ranges. the data were presented for the first time at the american academy of child and adolescent psychiatry, or aacap, 2020 virtual annual meeting. in the march 2021 post-period, nature digital medicine published the full results from the stars adjunct trial. vor biopharma inc. (puretech ownership: 8.6%) in the january 2021 post-period, vor announced that the fda had accepted the company’s ind application for vor33. vor plans to enroll the first patient in a phase 1/2a clinical trial for vor33 in the second quarter of 2021 and expects initial human engraftment and protection data from this trial to be reported in late 2021 or in the first half of 2022. in the february 2021 post-period, vor announced the pricing of its initial public offering of common stock on the nasdaq global market under the symbol “vor.” the aggregate gross proceeds to vor from the offering were approximately $203.4 million, before deducting the underwriting discounts and commissions and other offering expenses payable by vor. in july 2020, vor announced a $110 million series b financing to advance vor33 into clinical trials, deepen its portfolio and accelerate the validation of additional targets for its scientific platform. in november 2020, vor announced an exclusive licensing agreement with the national cancer institute, or nci, part of the national institutes of health, or nih, for intellectual property related to a clinical-stage anti-cd33 chimeric antigen receptor t cell, or car-t, therapy candidate, vcar33. vcar33 is currently being evaluated in a multi-site phase 1/2 clinical trial in young adults and pediatric patients with relapsed or refractory acute myeloid leukemia, or aml, and vor expects initial monotherapy clinical proof-of-concept data in 2022, depending on investigator’s timing of data release. in january 2020, vor held a pre-ind meeting with the fda to gather feedback to assemble the data package for a potential ind filing. in the january 2021 post-period, vor announced that the fda had accepted the company’s ind application for vor33. vor plans to enroll the first patient in a phase 1/2a clinical trial for vor33 in the second quarter of 2021 and expects initial human engraftment and protection data from this trial to be reported in late 2021 or in the first half of 2022. in the february 2021 post-period, vor announced the pricing of its initial public offering of common stock on the nasdaq global market under the symbol “vor.” the aggregate gross proceeds to vor from the offering were approximately $203.4 million, before deducting the underwriting discounts and commissions and other offering expenses payable by vor. in july 2020, vor announced a $110 million series b financing to advance vor33 into clinical trials, deepen its portfolio and accelerate the validation of additional targets for its scientific platform. in november 2020, vor announced an exclusive licensing agreement with the national cancer institute, or nci, part of the national institutes of health, or nih, for intellectual property related to a clinical-stage anti-cd33 chimeric antigen receptor t cell, or car-t, therapy candidate, vcar33. vcar33 is currently being evaluated in a multi-site phase 1/2 clinical trial in young adults and pediatric patients with relapsed or refractory acute myeloid leukemia, or aml, and vor expects initial monotherapy clinical proof-of-concept data in 2022, depending on investigator’s timing of data release. in january 2020, vor held a pre-ind meeting with the fda to gather feedback to assemble the data package for a potential ind filing. puretech health today released its annual report for the year ended december 31, 2020. in compliance with the financial conduct authority’s listing rule 9.6.3, the following documents have today been submitted to the national storage mechanism and will shortly be available for inspection at https://data.fca.org.uk/#/nsm/nationalstoragemechanism. annual report and accounts for the year ended december 31, 2020; and notice of 2021 annual general meeting. printed copies of these documents together with the form of proxy will be posted to shareholders. copies are also available electronically on the investor relations section of the company's website at https://investors.puretechhealth.com/financials-filings/reports. puretech’s 2021 annual general meeting (agm) will be held on may 27, 2021 at 11:00am edt / 4:00pm bst at puretech’s headquarters, which is located at 6 tide street, boston, massachusetts, united states. please note that in light of covid-19, it will not be possible for the directors to travel to the united kingdom. the company has therefore decided to hold the agm in the united states where most of the directors are resident. the company’s preference had been to welcome shareholders in person to the 2021 agm, particularly given the constraints faced in 2020 due to the covid-19 pandemic. however, at present, in light of the limits on international travel and the public health guidance issued in the uk and the us and in order to protect the wellbeing of puretech’s people and shareholders, the company is proposing to hold the agm as a closed meeting with the minimum attendance required to form a quorum. accordingly, shareholders will not be permitted to attend the agm in person but can be represented by the chair of the meeting acting as their proxy. the company continues to closely monitor the evolving situation in respect of covid-19 and its forthcoming agm. the health and welfare of the company's shareholders, as well as its employees and partners, is the number one priority. the company appreciates that a number of its shareholders are not resident or located in the united states and asks shareholders to participate in the agm by submitting any questions in advance and voting via proxy rather than attending in person. as such, any specific questions on the business of the agm and resolutions can be submitted ahead of meeting by e-mail to ir@puretechhealth.com (marked for the attention of dr. bharatt chowrira). shareholders are encouraged to complete and return their votes by proxy, and to do so no later than 4:00 pm (bst) on tuesday may 25, 2021. this will appoint the chair of the meeting as proxy and will ensure that votes will be counted even though attendance at the meeting is restricted. details of how to appoint a proxy are set out in the notice of agm. puretech will keep shareholders updated of any changes it may decide to make to the current plans for the agm. please visit the company’s website at www.puretechhealth.com for the most up to date information. about puretech health puretech is a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, including inflammatory, fibrotic and immunological conditions, intractable cancers, lymphatic and gastrointestinal diseases and neurological and neuropsychological disorders, among others. the company has created a broad and deep pipeline through the expertise of its experienced research and development team and its extensive network of scientists, clinicians and industry leaders. this pipeline, which is being advanced both internally and through puretech's founded entities is comprised of 26 products and product candidates, including two that have received fda clearance and european marketing authorization. all of the underlying programs and platforms that resulted in this pipeline of product candidates were initially identified or discovered and then advanced by the puretech team through key validation points based on the company's unique insights into the biology of the brain, immune and gut, or big, systems and the interface between those systems, referred to as the big axis. for more information, visit www.puretechhealth.com or connect with us on twitter @puretechh. cautionary note regarding forward-looking statements this press release contains statements that are or may be forward-looking statements, including statements that relate to the company's future prospects, developments, and strategies. the forward-looking statements are based on current expectations and are subject to known and unknown risks and uncertainties that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, our expectations regarding the potential therapeutic benefits of our product candidates and those of our founded entities, our expectations regarding 2021 milestones and timing, including with respect to clinical trial initiations and expected data readouts, our ability to broaden access to an international investor base, our cash runway and financial position as well as those risks and uncertainties described in the risk factors included in the regulatory filings for puretech health plc (including the risk factors in our 2020 annual report and accounts). these forward-looking statements are based on assumptions regarding the present and future business strategies of the company and the environment in which it will operate in the future. each forward-looking statement speaks only as at the date of this press release. except as required by law and regulatory requirements, neither the company nor any other party intends to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise. notes financial review reporting framework you should read the following discussion and analysis together with our consolidated financial statements, including the notes thereto, set forth elsewhere in this report. some of the information contained in this discussion and analysis or set forth elsewhere in this report, including information with respect to our plans and strategy for our business and financing our business, includes forward-looking statements that involve risks and uncertainties. as a result of many factors, including the risks set forth on pages 69 to 71 and in the additional information section from pages 191 to 227, our actual results could differ materially from the results described in or implied by these forward-looking statements. our audited consolidated financial statements as of december 31, 2020 and 2019 and for the years ended december 31, 2020, 2019 and 2018 have been prepared in accordance with international accounting standards in conformity with the requirements of the companies act 2006 and international financial reporting standards (ifrss) adopted pursuant to regulation (ec) no 1606/2002 as it applies in the eu. the consolidated financial statements also comply fully with ifrss as issued by the international accounting standards board (iasb). the following discussion contains references to the consolidated financial statements of puretech health plc, or the company, and its consolidated subsidiaries, together the group. these financial statements consolidate the company’s subsidiaries and include the company’s interest in associates and investments held at fair value. subsidiaries are those entities over which the company maintains control. associates are those entities in which the company does not have control for financial accounting purposes but maintains significant influence over financial and operating policies. where we have neither control nor significant influence for financial accounting purposes, we recognize our holding in such entity as an investment at fair value. for purposes of our consolidated financial statements, each of our founded entities are considered to be either a “subsidiary", an “associate” or an "investment held at fair value" depending on whether puretech health plc controls or maintains significant influence over the financial and operating policies of the respective entity at the respective period end date. for additional information regarding the accounting treatment of these entities, see note 1 to our consolidated financial statements included in this report. for additional information regarding our operating structure, see “—basis of presentation and consolidation” below. fair value of investments accounted for at fair value, does not take into consideration contribution from milestones that occurred after december 31, 2020, the value of our consolidated founded entities (vedanta, follica, sonde, akili, alivio, and entrega), our wholly owned programs, or our cash. business background and results overview the business background is discussed from pages 1 to 59, which describe in detail the business development of our wholly owned programs and founded entities. our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our wholly-owned or founded entities’ therapeutics candidates, which may never occur. our founded entities, gelesis, inc., or gelesis, and akili interactive labs, inc., or akili in which we lost control in 2019 and 2018, respectively, have products cleared for sale, but we and our controlled founded entities have not generated any revenue from product sales. we have deconsolidated a number of our founded entities during the past three fiscal years including akili, in 2018 and, vor biopharma inc., or vor, karuna therapeutics, inc., or karuna and gelesis inc., or gelesis, during 2019. we expect this trend to continue into the foreseeable future as our controlled founded entities raise additional funding. any deconsolidation affects our financials in the following manner: our ownership interest does not provide us with a controlling financial interest; we no longer control the founded entity's assets and liabilities and as a result we derecognize the assets, liabilities and non-controlling interests related to the founded entity from our consolidated statements of financial position; we record our non-controlling financial interest in the founded entity at fair value; and the resulting amount of any gain or loss is recognized in our consolidated statements of comprehensive income/(loss). we anticipate our expenses to continue to increase proportionally in connection with our ongoing development activities related to our preclinical and clinical programs within our wholly owned programs and controlled founded entities. in addition, having completed our u.s. listing in november 2020, we expect to incur additional costs associated with operating as a public company in the u.s. we also expect that our expenses and capital requirements will increase substantially in the near to mid-term as we: continue our research and development efforts; seek regulatory approvals for any therapeutic candidates that successfully complete clinical trials; add clinical, scientific, operational financial and management information systems and personnel, including personnel to support our therapeutic development and potential future commercialization claims; and operate as a u.s. public company. in addition, our internal research and development spend will increase in the foreseeable future as we may initiate clinical studies for lyt-100, lyt-200, lyt-210 and lyt-300, and as we continue to progress our glyphtm and orasometm technology platforms as well as our meningeal lymphatics discovery research program. in addition, with respect to our founded entities’ programs, we anticipate that we will continue to fund a small portion of development costs by strategically participating in such companies’ financings when it is in the best interests of our shareholders. the form of any such participation may include investment in public or private financings, collaboration and partnership arrangements and licensing arrangements, among others. our management and strategic decision makers consider the future funding needs of our founded entities and evaluate the needs and opportunities with respect to each of these founded entities routinely and on a case-by-case basis. as a result, we may need substantial additional funding to support our continuing operations and pursue our growth strategy. until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of public or private equity or debt financings or other sources, which may include monetization of certain of our interests in our founded entities and collaborations with third parties. we may be unable to raise additional funds or enter into such other agreements or arrangements when needed on favorable terms, or at all. if we fail to raise capital or enter into such agreements as, and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of one or more of our wholly-owned therapeutic candidates. measuring performance the financial review discusses our operating and financial performance, our cash flows and liquidity as well as our financial position and our resources. the results for each year are compared primarily with the results of the preceding year. reported performance reported performance considers all factors that have affected the results of our business, as reflected in our consolidated financial statements. core performance core performance measures are alternative performance measures (apm) which are adjusted and non-ifrs measures. these measures cannot be derived directly from our consolidated financial statements. we believe that these non-ifrs performance measures, when provided in combination with reported performance, will provide investors, analysts and other stakeholders with helpful complementary information to better understand our financial performance and our financial position from period to period. the measures are also used by management for planning and reporting purposes. the measures are not substitutable for ifrs results and should not be considered superior to results presented in accordance with ifrs. cash flow and liquidity consolidated cash reserves measure type: core performance definition: cash and cash equivalents, and short-term investments held at puretech health plc and consolidated subsidiaries (please refer to note 1 to our consolidated financial statements for further information with respect to our consolidated subsidiaries) why we use it: consolidated cash reserves is a measure that provides valuable additional information with respect to cash reserves available to fund the wholly owned programs and founded entities puretech level cash reserves measure type: core performance definition: cash and cash equivalents, and short-term investments held at puretech health plc and only wholly-owned subsidiaries (please refer to note 1 to our consolidated financial statements for further information with respect to our wholly-owned subsidiaries) why we use it: puretech level cash reserves is a measure that provides valuable additional information with respect to cash reserves available to fund the wholly owned programs and make certain investments in founded entities puretech level cash and cash equivalents measure type: core performance definition: cash and cash equivalents held at puretech health plc and only wholly-owned subsidiaries (please refer to note 1 to our consolidated financial statements for further information with respect to our wholly-owned subsidiaries) why we use it: puretech level cash and cash equivalents is a measure that provides valuable additional information with respect to cash and cash equivalents available to fund the wholly owned programs and make certain investments in founded entities consolidated cash reserves as of march 31, 2021 measure type: core performance definition: cash and cash equivalents, and short-term investments held at puretech health plc and consolidated subsidiaries as of march 31, 2021 why we use it: the measure includes cash outflows and inflows for the first quarter of 2021, particularly the sale of 1,000,000 common shares of karuna for aggregate proceeds of $118.0 million on february 9, 2021. further, the measure allows for a more current representation of the consolidated cash reserves (see above in table) as of the date of signing of our consolidated financial statements puretech level cash reserves as of march 31, 2021 measure type: core performance definition: cash and cash equivalents, and short-term investments held at puretech health plc and only wholly-owned subsidiaries as of march 31, 2021 why we use it: the measure includes cash outflows and inflows for the first quarter of 2021, particularly the sale of 1,000,000 common shares of karuna for aggregate proceeds of $118.0 million on february 9, 2021. further, the measure allows for a more current representation of the puretech level cash reserves (see above in table) as of the date of signing of our consolidated financial statements puretech level cash and cash equivalents as of march 31, 2021 measure type: core performance definition: cash and cash equivalents held at puretech health plc and only wholly-owned subsidiaries as of march 31, 2021 why we use it: the measure includes cash outflows and inflows for the first quarter of 2021, particularly the sale of 1,000,000 common shares of karuna for aggregate proceeds of $118.0 million on february 9, 2021. further, the measure allows for a more current representation of the puretech level cash and cash equivalents (see above in table) as of the date of signing of our consolidated financial statements covid-19 in december 2019, illnesses associated with covid-19 were reported and the virus has since caused widespread and significant disruption to daily life and economies across geographies. the world health organization has classified the outbreak as a pandemic. our business, operations and financial condition and results have not been significantly impacted during the year ended december 31, 2020 as a result of the covid-19 pandemic. in response to the covid-19 pandemic, we have taken swift action to ensure the safety of our employees and other stakeholders. we continue to monitor the latest developments regarding the covid-19 pandemic on our business, operations, and financial condition and results, and have made certain assumptions regarding the pandemic for purposes of our operational planning and financial projections, including assumptions regarding the duration and severity of the pandemic and the global macroeconomic impact of the pandemic. despite careful tracking and planning, however, we are unable to accurately predict the extent of the impact of the pandemic on our business, operations, and financial condition and results in future periods due to the uncertainty of future developments. we are focused on all aspects of our business and are implementing measures aimed at mitigating issues where possible including by using digital technology to assist operations for our r&d and enabling functions. recent developments (subsequent to december 31, 2020) on january 8, 2021, puretech participated in the second closing of vor’s series b preferred share financing. for consideration of $0.5 million, puretech received 961,538 shares. on february 9, 2021, vor closed its initial public offering of 9,828,017 shares at a price to the public of $18.00 per share. subsequent to the closing, puretech held 3,207,200.00 shares of vor common stock, representing 8.6% of vor common stock. on february 9, 2021, puretech health sold 1,000,000 common shares of karuna for aggregate proceeds of $118.0 million. following the sale puretech holds 2,406,564 shares of karuna common stock, representing 8.2% of karuna common stock. as of march 31, 2021, we had consolidated cash and cash equivalents of $486.5 million and puretech level cash and cash equivalents of $443.4 million. financial highlights as of: (in thousands) march 31, 2021 december 31, 2020 december 31, 2019 cash and cash equivalents 486,469 403,881 132,360 short-term investments — — 30,088 consolidated cash reserves 486,469 403,881 162,448 less: cash and cash equivalents held at non-wholly owned subsidiaries (43,072 ) (54,473 ) (41,840 ) puretech level cash reserves 443,397 349,407 120,608 less: short-term investments — — (30,088 ) puretech level cash and cash equivalents $ 443,397 $ 349,407 $ 90,520 basis of presentation and consolidation our consolidated financial information consolidates the financial information of puretech health plc, as well as its subsidiaries, and includes our interest in associates and investments held at fair value, and is reported in four operating segments as described below. basis for segmentation our directors are our strategic decision-makers. our operating segments are based on the financial information provided to our directors quarterly for the purposes of allocating resources and assessing performance. we have determined that each founded entity is representative of a single operating segment as our directors monitor the financial results at this level. when identifying the reportable segments we have determined that it is appropriate to aggregate multiple operating segments into a single reportable segment given the high level of operational and financial similarities across the entities. we have identi
