Category: lenS & thoughtS

Since the new FDA Commissioner Dr. Scott Gottlieb was sworn in on May 11, 2017, the traditionally cumbersome regulatory body has shown an unprecedented embracement for novelty in treatments and beyond.

Overarching guidelines:

• Digital Health Innovation Action Plan – July 2017
• Breakthrough Devices Program Guidance – draft issued October 2017, finalized December 2018
• FDA Unveils 6 New Draft Guidances on Gene Therapy – July 2018

Here is a roundup of those approvals

Novartis, Kymriah, first gene (transfer) therapy (first CAR-T) available in the United States

• August 30, 2017
• Biologics License Application (BLA) submitted on February 2, 2017
• Approval basis: the safety and efficacy of Kymriah were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within three months of treatment was 83 percent. (FDA statement)

Pear Therapeutics, the Reset app, first mobile application to treat substance use disorders (SUD)

• September 14, 2017
• de novo premarket review pathway
• Technology: the device delivers cognitive behavioral therapy to patients to teach the user skills that aid in the treatment of SUD and are intended to increase abstinence from substance abuse and increase retention in outpatient therapy programs. The system is intended to be used in conjunction with outpatient therapy and in addition to a contingency management system, a widely-used program for treating SUD that uses a series of incentives to reward patients for adherence to their treatment program.
• Approval basis: a multi-site, unblinded 12-week clinical trial of 399 patients who received either standard treatment or standard treatment with the addition of a desktop-based version of Reset which could be accessed at the clinic or at home. The data showed a statistically significant increase in adherence to abstinence for the patients with alcohol, cocaine, marijuana and stimulant SUD in those who used Reset, 40.3 percent, compared to the patients who did not, 17.6 percent. The clinical trial did not demonstrate the effectiveness of using the Reset device in patients reporting opioids as their substance of abuse. (FDA statement)

Memorial Sloan Kettering Cancer Center,  IMPACT test, first tumor-profiling laboratory-developed test to receive authorization through the FDA

• November 15, 2017
• de novo premarket review pathway
• Technology: the IMPACT test uses next-generation sequencing (NGS) to rapidly identify the presence of mutations in 468 unique genes, as well as other molecular changes in the genomic makeup of a person’s tumor.
• Approval basis: results indicated that the assay is highly accurate (greater than 99 percent) and capable of detecting a mutation at a frequency of approximately 5 percent (range of 2-5 percent). Additionally, detection of certain molecular changes (microsatellite instability) using the IMPACT test was concordant more than 92 percent of the time across multiple cancer types in 175 cases, when compared to traditional methods of detection.
• Along with this authorization, the FDA is also establishing a Class II regulatory pathway for the review of other NGS-based tumor profiling tests for use in patients diagnosed with cancer. Class II designation allows these types of tests to be eligible to use the FDA’s 510(k) clearance process, either by submitting the application. (FDA statements)

Proteus Digital Health x Otsuka Pharma, Abilify MyCite, first drug in the U.S. with a digital ingestion tracking system

• November 13, 2017
• New Drug Application (NDA) dated and received June 26, 2015
• Technology: the system works by sending a message from the pill’s sensor to a wearable patch. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smart phone. Patients can also permit their caregivers and physician to access the information through a web-based portal.
• Approval basis: Abilify was first approved by the FDA in 2002 to treat schizophrenia. The ingestible sensor used in Abilify MyCite was first permitted for marketing by the FDA in 2012. (FDA statement)

Spark Therapeutics, Luxturna, first (directly administered) gene therapy approved in the U.S. to target a disease caused by mutations in a specific gene

• December 19, 2017
• Biologics License Application (BLA) dated April 26, 2017, and received May 16, 2017
• Approval basis: The efficacy of LUXTURNA in the Phase 3 study was established based on the multi-luminance mobility test (MLMT) score change from baseline to one year. LUXTURNA Phase 3 clinical study results showed a statistically significant difference between the intervention group (n=21) and control participants (n=10) at one year in median bilateral MLMT score change (intervention minus control group difference of 2; p=0.001) and median first-treated eye MLMT score change (intervention minus control group difference of 2; p=0.003). (Spark press release)
• FDA statement

Loxo Oncology, Vitrakvi, first time that an entirely new treatment has received a tumor-agnostic indication at its initial approval

• November 26, 2018
• covered in a previous blog: Loxo and Pan-Cancer Treatments

Apple, the ECG app (with Apple Watch), first FDA clearance for retail ECG watch technology

• September 11, 2018
• De Novo clearance from the Center for Devices and Radiological Health, classified as Class II under the generic name electrocardiograph software for over-the-counter use
• Technology: the ECG app determines the presence of atrial fibrillation (AFib) or sinus rhythm on a classifiable waveform
• FDA statement
• FDA letter to Apple
• covered in a previous blog: New Era of Medical Grade Consumer Device

• January 17, 2019 update: Alphabet’s life sciences unit Verily received 510(k) clearance from FDA as a Class II medical device for its on-demand ECG feature

Anti-aging is a centuries-long problem and we don’t have an answer.

Here is a summary of current notable efforts that might provide some sort of solution.

Biopharma/Therapeutics Approach

Unity Biotechnology – eliminate senescent cells

• [Darren Baker] & [Jan van Deursen], inventors on patents licensed to Unity; and J.M.v.D. is a co-founder of Unity
  • November 2011, a foundational paper published on Nature – Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
  • February 2016, another foundational paper published on Nature – Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
  • November 2016, $116 million Series B, with an additional closing of $35 million in August 2017
• [Judith Campisi], co-founder of Unity
  • a leading figure in the biology of aging since the early 1990s
  • her research is on the role of cellular senescence in cancer and other age-related diseases
  • a review on Four faces of cellular senescence in 2011
  • a MIT Technology Review conversation with Camplisi
• March 2018, $55 million Series C, with an additional closing of $5 million in April
• May 2018, $85 million IPO
• Pipeline (Dec. 2018)

• Lead candidate UBX0101, a first-in-class senolytic molecule
  • Preclinical – April 2017, a paper published on Nature Medicine, Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment, the selective elimination of senescent cells in the knees of mice, and slow of the progression of disease, reduced pain, and induced cartilage production in human knee tissue grown in culture.
  • Phase I
    • IND cleared by FDA in April 2018
    • clinical trial
    • First patient dosed in June 2018
    • Cohort expansion in December 2018 with a higher dose (4 mg), compared with previous cohorts 1 through 5 (0.1 to 2 mg dose)
• UBX1967
  • January 2019, completed license agreement with Ascentage Pharma, granting Unity the exclusive worldwide development and commercialization rights and non-exclusive manufacturing rights outside of Greater China (China, Hong Kong, Macau and Taiwan) for UBX1967 in all non-oncology indications. Inside Greater China, UNITY is obligated to commercialize UBX1967 through a joint venture with Ascentage Pharma. The UBX1967 License Agreement also grants UNITY the right to continue its preclinical development efforts with respect to another Ascentage Pharma-controlled Bcl-2 inhibitor compound that will serve as a back-up to UBX1967.
  • Per the 2016 pact, should Unity choose to license at least one more products, the Chinese biotech will gain a total of 1,333,338 shares
  • plans to file an IND application for UBX1967 in the second half of 2019

Calico – A previous google company

• Founded in 2013, Calico started within Google (later Alphabet) and soon jump-started with huge fundings – a $1.5 billion initiative/collaboration in September 2014 with Abbvie. “AbbVie and Calico will each initially provide up to $250 million to fund the collaboration with the potential for both sides to contribute an additional $500 million.”
• In June 2018, the collaboration was extended with another $1 billion. “AbbVie and Calico will each commit to contribute an additional $500 million to the collaboration.”
• It was also cited that “since 2014, the collaboration between the two companies has produced more than two dozen early-stage programs addressing disease states across oncology and neuroscience and yielded new insights into the biology of aging.”

samumed

• Raised $438M in August 2018 at a valuation of $12 billion
• 8 programs in its pipeline: two Phase II drugs, five in Phase I, and one preclinical (Endpoints reported in Aug. 2018); one of the Phase II drug in Androgenetic Alopecia has moved to Phase III (Jan. 2019)

Napa Therapeutics

• Buck Institute + Juvenescence + Insilico Medicine
• Formed in August 2018
• based on research in NAD metabolism conducted in the lab of Eric Verdin, MD, President and CEO of the Buck Institute

Data Approach

Juvenescence AI

• A subsidiary of Juvenescence, a joint effort of Juvenescence + Insilico Medicine
• Formed in July 2017

Human Longevity

• Was valued at $1.6 billion in 2017 with fundings from Celgene, Illumina, GE Ventures, etc.
• Declined to a valuation of $310 million according to a WSJ report

Portfolio Approach

Juvenescence

• Raised $50 million Series A in June 2018 and $46 million Series B-1 in Jan 2019
• Investments/Subsidiaries
  • Juvenescence AI (see above)
  • Napa Therapeutics (see above)
  • August 2018, $43.2 million cash + note 50/50 to BioTime (NYSE: BTX) for AgeX shares
  • June 2018, $5 million investments in AgeX Therapeutics
  • May 2018, $3 million investment in LyGenesis
  • Insilico Medicine

Life Biosciences

• Jan. 2019 Series B of $50 million
• co-founded in 2017 by David Sinclair and Tristan Edwards
• 8 Subsidiaries
  • Prana Biotechnology (an initial $7.5 million investment in Jan.2019)
  • Lua, HIPAA-compliant medical technology platform (acquired in Oct. 2018)
  • Senolytic Therapeutics acquired at a very early stage
  • Jumpstart Fertility acquired at a very early stage
  • the other four were formed in-house (Selphagy Tx, Spotlight Biosciences, Continuum Biosciences, Animal Biosciences)

Somehow, reminded me of Theranos… also an area that might not be reguated by FDA… (Ageing is not a disease by FDA’s definition) and some are backed by non-traditional biotech VC firms… But most seemed to be more experienced and sophisticated in biology and medicine (than Theranos’ average).