Puretech Ownership1
Therapeutic Candidate2
Initial Indication(s)
Stage of Development
23.4% Equity
EndeavorRx®3 (AKL-T01)
ADHD
Pre-launch
Cognitive dysfunction in depression
Major depressive disorder
Discovery and research
Cognitive dysfunction in multiple sclerosis
Multiple sclerosis
Discovery and research
Autism spectrum disorder
Autism spectrum disorder
Discovery and research
Post-COVID cognitive dysfunction
COVID brain fog
Discovery and research
1 As of June 30, 2021, PureTech's percentage ownership of Akili is approximately 23.4% on a diluted basis. This calculation of PureTech's holding includes issued and outstanding shares as well as options and warrants to purchase shares, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.
2 These therapeutic candidates are regulated as devices and their development has been approximately equated to phases of clinical development. With the exception of EndeavorRx, candidates are investigational and have not been cleared by the FDA for use in the United States.
3 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. Patients who engage with EndeavorRx demonstrate improvements in a digitally assessed measure Test of Variables of Attention (TOVA) of sustained and selective attention and may not display benefits in typical behavioral symptoms, such as hyperactivity. EndeavorRx should be considered for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder. EndeavorRx is available by prescription only. It is not intended to be used as a stand-alone therapeutic and is not a substitution for a child’s medication.
EndeavorRx®
Advancing digital treatments to target cognitive dysfunction associated with conditions across neurology and psychiatry
- Akili is a leading digital therapeutics company, combining scientific and clinical rigor with the ingenuity of the tech industry while pursuing the goal of changing how medicine is developed, delivered and experienced. Akili is pioneering the development of treatments designed to have direct therapeutic activity, delivered not through a traditional pill but via a high-quality video game experience. Akili is evaluating a number of technologies and potential new digital medicines designed to target neural systems to improve associated cognitive functions.
- Akili’s EndeavorRx treatment is based on a patented technology that is designed to deploy sensory and motor stimuli that target and activate the neurological systems known to play a key role in certain cognitive functions, including attentional control. Akili’s approach aims to improve cognitive impairment and related symptoms through improving neural processing at the functional neurological level. The treatment is delivered through an immersive video game, resulting in non-invasive, patient-friendly medicine that can be used at home.
- By combining high-quality neurological and clinical science, and consumer-grade entertainment, Akili is seeking to produce a new type of medical product that can potentially offer safe, effective, scalable and personalized treatments for patients across a range of neuropsychiatric conditions and allow patients to experience medicine in a new way.
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Program Discovery Process by the PureTech Team
- We were interested in identifying novel approaches to measure and improve cognition in a safe and non-invasive manner. We engaged with leading neuroscientists and clinicians who had been studying the effects of video games on cognition and the underlying neural processes accessible by sensory stimulation, and we identified and in-licensed from the University of California, San Francisco (UCSF) the intellectual property invented by Dr. Adam Gazzaley, M.D., Ph.D., Professor of Neurology, Psychiatry and Physiology at UCSF and the inventor of the SSME platform technology, in October 2013 before his work was published as a cover story in the journal Nature. We then collaborated with Dr. Gazzaley to translate the underlying academic device into a medical intervention, including overseeing the initial product development and design and the implementation of the initial POC studies. We helped to build development and commercial teams and raise funds. One of the core PureTech team members who helped lead the identification and platform development is now the Chief Executive Officer of Akili.
- Akili’s FDA-cleared product, EndeavorRx™, is based on a platform technology exclusively licensed from UCSF. The proprietary platform targets cognitive interference processing while also adapting difficulty automatically in real-time, allowing individuals of wide-ranging ability levels to interact with the product in their homes without the need for physician calibration or additional hardware. Dr. Gazzaley currently serves as the Chief Scientific Advisor and a board member of Akili. Daphne Bavelier, Ph.D., Associate Professor in the Department of Brain and Cognitive Sciences at the University of Rochester and at the University of Geneva, is a co-founding scientific advisor.
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Patient Need & Market Potential
- Cognitive dysfunction is a key feature of many neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). The treatment of the cognitive dysfunction associated with these conditions is only partially served, or not served at all, by currently available medications or by in-person behavioral therapy. There are approximately 6.4 million pediatric ADHD patients in the United States and this market – and other markets where Akili’s cognitive dysfunction targeting products may address the cognitive dysfunction associated with neuropsychiatric disorders – represent significant potential opportunities for the company.
- Evidence is mounting on long-term neurological and cognitive symptoms that can persist in some COVID-19 patients after initial diagnosis, even after the virus is no longer detected in the body. A study published in Neuropsychopharmacology led by Drs. Abhishek Jaywant and Faith Gunning at Weill Cornell Medicine and NewYork-Presbyterian found that difficulties in attention, multitasking, and processing speed were common in hospitalized patients recovering from COVID-194. Of the patients in their study, 81 percent exhibited some degree of cognitive impairment4. Recent research also shows these cognitive impairments may persist posthospitalization and commonly occur in “post-COVID long haulers” or “long COVID” patients. These impairments can have a significant impact on survivors’ daily functioning and quality of life, impacting the ability of most COVID-19 long haulers to work for six months or more according to a recent study5.
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Milestones Achieved & Development Status
- In September 2021, Akili announced topline results of a Phase 2 study of SDT-001 (Japanese version of AKL-T01). The study, conducted by Akili partner Shionogi, was designed to evaluate the feasibility, safety and efficacy of the digital therapeutic in children with ADHD and to inform the design of a potential pivotal study. To enable this clinical trial, Akili localized its AKL-T01 technology for use in the Japanese market, which included adapting for language and culture and establishing infrastructure in Japan to support the product. Results show the treatment was well-received by patients and demonstrated improvements in ADHD inattention symptoms consistent with those seen across previous studies of AKL-T01.
- In August 2021, Akili and Australian digital health company TALi® (ASX:TD1), completed an agreement for Akili to license TALi's technology designed to address early childhood attention impairments. The companies plan to work together to execute clinical trials of the TALi technology in pediatric ADHD in the United States and pursue FDA regulatory clearance. Under the terms of the agreement, Akili will lead potential U.S. commercialization and roll-out.
- In July 2021, Akili introduced new gaming features and functionalities to its EndeavorRx treatment. The enhancements were based on the latest trends in video game development and informed by user insights collected across multiple forums, including playtesting, workshops, in-depth interviews with patients and caregivers, surveys, gameplay data and longitudinal research. The new gameplay features are being released as Akili begins its go-to market approach to bring EndeavorRx to families and healthcare professionals at scale.
- In June 2020, Akili announced that the FDA has granted clearance to market EndeavorRx as a prescription treatment for improving attention function in children with 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 issue7.
- 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.
- Akili’s EndeavorRx was evaluated in a multi-center, randomized, blinded, controlled pivotal study in 348 pediatric ADHD patients. In this study, AKL-T01 achieved its primary endpoint, showing a statistically significant change in the Attention Performance Index, a composite score of attention from the Test of Variables of Attention (T.O.V.A.®) compared to an expectancy matched digital control (p=0.006). There were no serious adverse events (SAEs) or discontinuations. Of participants using EndeavorRx, 9.2 percent experienced TRAEs which were mild and included frustration (2.8 percent) and headache (1.7 percent). Mean patient compliance with AKL-T01 was 83 percent of instructed use. Subjective secondary outcome measures, including the ADHD Rating Scale and the Impairment Rating Scale, showed statistically significant improvements in both the treatment and control groups and there was no statistically significant separation on those measures between groups.
- In April 2021, 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 IRS from baseline after one month of treatment (p<0.001) in both children taking stimulant medications and in those not taking stimulants. In the March 2021 post-period, Nature Digital Medicine published the full results from the STARS Adjunct trial.
- In March 2019, Akili entered into a strategic partnership with Shionogi for the development and commercialization of AKL-T01 (in development for children with ADHD) and AKL-T02 (in development for children with ASD) in Japan and Taiwan. Under the terms of the agreement, Akili will build and own the platform technology and received upfront payments totaling $20 million with potential milestone payments for Japan and Taiwan commercialization of up to an additional $105 million in addition to royalties. Akili and Shionogi have initiated a clinical study in preparation for a regulatory submission in Japan.
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Expected Milestones
- Akili expects to continue expanding its pre-launch activities to bring EndeavorRx to families and healthcare professionals.
4 Jaywant et al. Neuropsychopharmacol. (2021).
5 David et al. Preprint. (2020).
Multiple IRBs have determined AKL-T01 to be a non-significant risk device. Akili has obtained IRB approval independently or in collaboration with independent clinical research institutions for all past and ongoing human data collection for clinical research in the United States. We do not control the clinical or regulatory development of Akili’s product candidates. We do not have a direct interest in Akili’s therapeutic or therapeutic candidates. Our interest in Akili’s therapeutic and therapeutic candidates is limited to our equity interest in Akili and any potential appreciation in the value of such equity interest, and we do not control the clinical or regulatory development of Akili’s therapeutic candidates. Akili is well-protected with a robust intellectual property portfolio. Akili was incorporated in February 2012.
Akili received clearance from the FDA as well as European marketing authorization for the first prescription treatment delivered through a video game, EndeavorRx. 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 issue3.
Press Releases
PureTech Founded Entity Akili Announces Topline Results from Shionogi Phase 2 Study in Japan
September 29, 2021
PureTech Founded Entity Akili Enters Strategic Licensing Agreement with TALi, Extending Akili Portfolio and Industry Leadership in Prescription Digital Therapeutics for Cognitive Impairments
August 17, 2021
PureTech Founded Entity Akili Releases New Gameplay Features in the First and Only FDA-Cleared Video Game Treatment for Children with ADHD
July 22, 2021
PureTech Founded Entity Akili Secures $160 Million in Financing; Poised to Deliver on the Promise of Digital Therapeutics
May 26, 2021
PureTech Founded Entity Akili Collaborates with Weill Cornell Medicine, NewYork-Presbyterian Hospital and Vanderbilt University Medical Center to Study Digital Therapeutic AKL-T01 as Potential Treatment for Patients with COVID Brain Fog
April 7, 2021
PureTech Founded Entity Akili Announces the Results of EndeavorRx™ Clinical Study in Pediatric ADHD Published in Nature Digital Medicine
March 26, 2021
PureTech Founded Entity Akili Announces Presentation of New Outcome Data for Digital Therapeutic EndeavorRx™ in Paediatric ADHD
October 21, 2020
PureTech Founded Entity Akili Announces Appointment of Chief Marketing Officer
October 7, 2020
PureTech Founded Entity Akili Receives Approval to Market EndeavorRx™ in Europe as a Digital Treatment for Children with ADHD
June 23, 2020
PureTech Founded Entity Akili Announces FDA Clearance of EndeavorRx™ for Children with ADHD, the First Prescription Treatment Delivered Through a Video Game
June 16, 2020
PureTech Founded Entity Akili Announces ENDEAVOR™ Digital Attention Treatment is Now Available for Children with Attention Deficit Hyperactivity Disorder (ADHD) under FDA’s COVID-19 Enforcement Discretion Guidance
April 22, 2020
The Lancet Digital Health Publishes Akili AKL-T01 ADHD Pivotal Study Results
February 25, 2020
PureTech Affiliate Akili Announces New AKL-T01 Study Achieved Primary Endpoint in Children with ADHD
January 15, 2020
PureTech Affiliate Akili Announces AKL-T03 Achieved Primary Endpoint, Improving Cognitive Impairments in Major Depressive Disorder Trial
December 13, 2019
PureTech Health Affiliate Akili Appoints Chief Financial Officer and General Counsel to Leadership Team
April 11, 2019
PureTech’s Independent Affiliate Akili Announces Partnership with Shionogi to Develop and Commercialise Digital Therapeutics in Certain Asian Markets
March 7, 2019
Effectiveness of a digital therapeutic as adjunct to treatment with medication in pediatric ADHD
March 2021
A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial
February 2020
Characterizing cognitive control abilities in children with 16p11.2 deletion using adaptive ‘video game’ technology: a pilot study
September 2016
The use and effectiveness of mobile apps for depression: Results from a fully remote clinical trial
February 2016
Games to do you good
February 2013