On October 17, 2023 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, reported that members of the management team will participate in fireside chats at two upcoming investor conferences (Press release, PureTech Health, OCT 17, 2023, View Source [SID1234636071]). Webcasts of the presentations will be available at View Source

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Jefferies London Healthcare Conference

Presenters: Daphne Zohar, Founder and Chief Executive Officer, and Julie Krop, M.D., Chief Medical Officer

Date: Wednesday, November 15, 2023

Evercore ISI 6th Annual Healthcare Conference

Presenters: Daphne Zohar, Founder and Chief Executive Officer, and Julie Krop, M.D., Chief Medical Officer

Date: Wednesday, November 29, 2023

Commenting on the third quarter progress, Daphne Zohar, Founder and Chief Executive Officer of PureTech, said:

"It has been a very productive third quarter across our Wholly Owned Pipeline and Founded Entities, with multiple milestones reached as well as the continued progression toward several more major catalysts by the end of this year.

"Across our Wholly Owned Pipeline, we are looking forward to data from two clinical trials by the end of 2023, including data from the Phase 1b trial of LYT-200 in oncology, and the Phase 2a trial of LYT-300 in a validated clinical model of anxiety.

"Recently, we have been increasing our focus on our central nervous system (CNS) programs, including LYT-300 and LYT-310, that originated from our GlyphTM technology platform. Our increased focus reflects the historic success we’ve had in CNS by enabling drugs with proven human efficacy to realize their full therapeutic potential by applying an innovative solution to a previous limitation. As a result, we have now generated an additional two programs based on our Glyph platform, expanding our CNS pipeline to seven programs.

"Our increasing focus on this proven strategy for treating brain diseases builds on the success we had with KarXT and we are also pleased to note the important milestone of Karuna’s submission of a New Drug Application to the U.S. Food and Drug Administration (FDA) for KarXT for the treatment of schizophrenia. If approved, KarXT, invented at PureTech, will be the third therapeutic candidate to be taken from inception at PureTech to FDA regulatory approval.

"We plan to provide more guidance on our capital allocation and returns strategy in the fourth quarter. We look forward to another catalyst-rich quarter and continuing to deliver on our mission of changing the lives of patients with devastating diseases."

Key Highlights & Progress

Wholly Owned Programs

· LYT-100 (deupirfenidone), is currently in development for the treatment of conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis (IPF).

o Progressed Phase 2b dose-ranging trial of LYT-100 (deupirfenidone) in patients with idiopathic pulmonary fibrosis (IPF). Topline results are expected in 2024. We plan to pursue a streamlined development program for LYT-100 in IPF and are using the same endpoints that have supported past approvals. Pending positive clinical and regulatory feedback, we intend to advance the program into a Phase 3 trial. We believe the results of the Phase 2b trial, together with a Phase 3 trial, could serve as the basis for registration in the U.S. and other geographies.

o Presented expanded data from a completed trial of LYT-100 in healthy older adults, which informed the two doses selected for the ongoing, global Phase 2b dose-ranging trial of LYT-100 (ELEVATE IPF) in patients with IPF. In addition to supporting the improved tolerability of LYT-100 versus the FDA-approved dose of pirfenidone, the new data presented supported the selection of a higher dose of LYT-100 with the potential for improved efficacy that is now being evaluated in ELEVATE IPF.

· LYT-300 (oral allopregnanolone) is an oral prodrug of allopregnanolone, enabled by our GlyphTM technology platform, that is currently in development for the treatment of a range of neurological and neuropsychological conditions, including anxiety, mood disorders and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).

o Progressed a Phase 2a proof-of-concept trial of LYT-300 using a validated clinical model of anxiety in healthy volunteers. Results are expected by the end of 2023.

o Awarded up to $11.4 million from the U.S. Department of Defense to advance LYT-300 for Fragile X-associated Tremor/ Ataxia Syndrome (FXTAS). The Phase 2 trial of LYT-300 in FXTAS in collaboration with the University of California, Davis is expected to initiate in 2024.

· LYT-310 (oral cannabidiol [CBD]), is currently in development for the treatment of epilepsies and other neurological indications.

o A Phase 1 clinical trial of LYT-310 is expected to begin in the fourth quarter of 2023.

· LYT-200 (anti-galectin-9 mAb) is currently in development for the treatment of metastatic/locally advanced solid tumors, including urothelial and head and neck cancers, and hematological malignancies, such as acute myeloid leukemia (AML).

o Progressed a Phase 1b trial of LYT-200 in combination with tislelizumab in urothelial and head and neck cancers. Topline results are expected in 2024.

o Progressed a Phase 1b trial evaluating LYT-200 as a single agent for the treatment of AML. Initial results from a subset of patients are expected by the end of 2023.

Founded Entities

· Karuna Therapeutics (Nasdaq: KRTX) (Karuna) submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for the potential approval of KarXT for the treatment of schizophrenia.

· Vedanta dosed the first patient in the Phase 2 COLLECTiVE202 clinical study of VE202 for the treatment of ulcerative colitis. The FDA also granted Fast Track designation to VE202. The phase 3 RestoratiVE303 pivotal study of VE303, designed for the prevention of recurrent Clostridioides difficile infection, is expected to initiate in the coming months.

· Akili, Inc. (Nasdaq: AKLI) (Akili) announced its strategic plan to transition from a prescription to a non-prescription business model. Akili is on track to submit its adult clinical trial data later this year to the FDA for over-the-counter (OTC) authorization of EndeavorOTC, and is planning to submit data to the FDA to convert its pediatric prescription product, EndeavorRxⓇ, to OTC in 2024.

· Sonde Health has partnered with Together, an AI-based health assistant, to provide enhanced mental health detection and monitoring through its new Mental Vitals feature. This collaboration integrates Sonde’s technology into the Together app, allowing users to access advanced voice analysis for early detection of symptoms related to depression and anxiety.

· PureTech will not move forward with the contemplated plan of merger with Gelesis and will instead focus on other strategic business initiatives.

On October 17, 2023 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that the company will present two poster presentations at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 taking place October 20-24, 2023, in Madrid, Spain (Press release, ORIC Pharmaceuticals, OCT 17, 2023, View Source [SID1234636070]). The presentations will highlight the initial Phase 1b clinical data for ORIC-114 in EGFR/HER2 exon 20 mutated cancers and new preclinical data for ORIC-114 demonstrating activity against additional atypical mutations in EGFR.

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In conjunction with the ESMO (Free ESMO Whitepaper) presentations, ORIC will host a conference call and webcast on Saturday, October 21, 2023, at 9:00 a.m. ET. Management will be joined by Dr. Alexander Spira, Clinical Director, NEXT Oncology-Virginia, who will share his perspective on the initial data from the Phase 1b study and the potential of ORIC-114 to treat EGFR/HER2 exon 20 mutated cancers.

Details of the ESMO (Free ESMO Whitepaper) poster presentations are as follows:

Title: A Global Phase 1b Study of ORIC-114, a Highly Selective, Brain Penetrant EGFR and HER2 Inhibitor, in Patients with Advanced Solid Tumors Harboring EGFR Exon 20 or HER2 Alterations
Poster #: 1333P
Poster Session: NSCLC, metastatic
Date & Time: Monday, October 23, 2023, at 9:00 a.m. CEST

Title: Preclinical Activity of ORIC-114, a Highly Selective, Brain Penetrant,
Irreversible Kinase Inhibitor, Against Atypical Mutations in EGFR
Poster #: 1345P
Poster Session: NSCLC, metastatic
Date & Time: Monday, October 23, 2023, at 9:00 a.m. CEST

Full abstracts are available for public viewing via the ESMO (Free ESMO Whitepaper) website. ePosters will be available Saturday, October 21, 2023, at 9:00 a.m. CEST.

Conference Call and Webcast Details

To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

On October 17, 2023 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported that it has entered into a strategic collaboration and licensing agreement with global healthcare leader Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug (Press release, Monte Rosa Therapeutics, OCT 17, 2023, View Source [SID1234636069]).

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"We are excited to partner with Roche, a leading healthcare and one of the world’s top oncology companies. Our QuEEN discovery engine, a highly validated and industry-leading molecular glue degrader platform, has been the cornerstone for Monte Rosa’s success, driving the discovery and development of our exquisitely selective MGDs successfully into the clinic. This collaboration will enable and accelerate expansion of our platform into neuroscience and additional areas of oncology. We believe our decision to partner with Roche, a company that shares our vision and drive, will amplify our collective strengths and capabilities to accelerate the development of transformative treatments for patients across several indications," said Markus Warmuth, M.D., CEO of Monte Rosa Therapeutics.

James Sabry, M.D., Ph.D., Global Head of Pharma Partnering at Roche, added: "We believe that molecular glue degraders are a powerful new class of small molecules that target disease-related proteins that traditional approaches have been unable to address. Together with Monte Rosa, we look forward to tackling high-value targets in both oncology and neuroscience with the goal of unlocking new therapeutic possibilities."

Under the terms of the agreement, Monte Rosa Therapeutics will receive an upfront payment of $50 million, and is eligible to receive future preclinical, clinical, commercial and sales milestone payments that could exceed $2 billion, as well as tiered royalties. The parties also agreed on a mechanism to expand the collaboration on multiple targets within the first two years. In that case, additional payments for nomination, preclinical, clinical, commercial and sales milestones are due, as well as tiered royalties on the resulting products. Monte Rosa Therapeutics will lead discovery and preclinical activities against multiple select cancer and neurological disease targets to a defined point. Roche gains the right to exclusively pursue further preclinical and clinical development of the compounds. Monte Rosa retains full ownership of its pipeline programs.

On October 17, 2023 LIXTE Biotechnology Holdings, Inc. (Nasdaq: LIXT and LIXTW) reported that it has signed an agreement to expand its collaboration with the Netherlands Cancer Institute (NKI) and Oncode Institute to study drug synergies of LIXTE’s lead clinical compound, LB-100, with immunotherapy in various cancers (Press release, Lixte Biotechnology, OCT 17, 2023, View Source [SID1234636068]). The new agreement also will seek to find synthetic lethal combinations in additional cancer types.

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The two-year extension agreement follows successful collaboration during the past two years to identify the most promising drugs to be combined with LB-100 for treating colon cancer, as well as to identify the specific molecular mechanisms underlying the identified combinations in order to provide a rationale to test these combinations in clinical trials.

NKI, based in Amsterdam, Netherlands, is among the world’s leading comprehensive cancer centers. Oncode Institute, headquartered in Utrecht, Netherlands, is a major independent cancer research center dedicated to translating research into practice and bringing discoveries into a clinic setting more quickly.

NKI’s René Bernards, Ph.D., and his group – using genome-wide functional genetic techniques to identify effective drug combinations, new drug targets and mechanisms of resistance to cancer drugs – have identified a number of drug combinations that are now approved for patients or in advanced clinical development. Prof. Bernards is a professor of molecular carcinogenesis and has been a member of LIXTE’s board of directors since June 2022.

"We are excited to continue and extend our work with LIXTE on additional types of cancer, as we look to identify the most powerful drug combinations of LB-100 for various cancer therapies," Prof. Bernards said. "In addition, we look forward to working with LIXTE to investigate the molecular mechanism of synergy of LB-100 with immune checkpoint therapy and testing of novel PP2A inhibitor molecules in cancer models."

Bas van der Baan, the recently appointed Chief Executive Officer and President of LIXTE, added, "The collaboration with Prof. Bernards and his team provides us with unique insights in our efforts to identify promising therapy combinations for LB-100 and a more targeted approach to cancer treatment."

On October 17, 2023 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported results from its registration-directed AIM-HN study of tipifarnib in patients with HRAS mutant head and neck squamous cell carcinoma (HNSCC) whose disease is recurrent or metastatic and has progressed after prior therapy (Press release, Kura Oncology, OCT 17, 2023, View Source [SID1234636067]).

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These clinical results are being featured during a late-breaking oral session at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Madrid, Spain, in a presentation titled, "A phase 2 study evaluating tipifarnib in mHRAS, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (AIM-HN study)." The abstract is now available on the ESMO (Free ESMO Whitepaper) website and the presentation will be available in the Posters and Presentations section on Kura’s website at the start of the poster session on Saturday, October 21, 2023 at 10:15AM CEST.

As of the data cutoff on June 15, 2023, 59 patients with R/M HRAS mutant HNSCC were enrolled, of whom 50 had high HRAS mutant variant allele frequency (VAF)1 and 38 were evaluable for efficacy. The following table compares response assessed between the investigators and the independent review facility (IRF), in the modified intent to treat (mITT) high VAF population2.

Investigator
Assessment (n=50) Independent
Review Facility (n=50)
Best Overall Response, n (%)
Confirmed Complete Response (CR) 1 (2)​ 1 (2)​
Confirmed Partial Response (PR) 14 (28)​ 9 (18)​
Stable Disease (SD) 17 (34)​ 14 (28)​
Progressive Disease (PD) 6 (12)​ 14 (28)​
Not Evaluable (NE) 12 (24)​ 12 (24)​
ORR, n (%) [95% CI] ​ 15 (30) [0.18, 0.45]​ 10 (20) [0.10, 0.34]​
mDoR, months [95% CI]​ 5.6 [3.88, 9.23]​ 6.5 [3.88, -]​
mPFS, months [95% CI]​ 3.7 [2.60, 5.55]​ 2.6 [1.87, 4.40]​
*ORR, objective response rate; -, not calculable; mDoR, median duration of response; mPFS, median progression free survival; CI, confidence interval.

Both assessments by investigators and IRF observed one patient achieving a CR on treatment. Patients had a median of two prior lines of therapy (range 0-6) in the recurrent/metastatic setting and robust activity was seen in second line treatment and beyond with greater activity observed in the second line versus the third line and subsequent treatments. The ORR in second line treatment was 29% [0.13, 0.51] in the IRF assessment. The ORR for three FDA-approved therapies for the treatment of HNSCC in the second line range from 13-16%.

"The results from the AIM-HN study are encouraging as they demonstrate meaningful clinical benefit of tipifarnib in a subset of HNSCC for which there are currently no other targeted therapies in development, and a significant unmet need exists for the population," said Alan Ho, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center and principal investigator of the study. "We are grateful to the patients and their families for their trial participation and for the scientific community who have contributed to this pivotal research in an effort to impact patients’ lives."

Patients in the AIM-HN trial received tipifarnib at a dose of 600 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles. Tipifarnib was generally well-tolerated with a manageable safety profile. The most common grade 3 or 4 treatment-related adverse events (TRAEs) seen in at least 10% of patients were cytopenias and TRAEs led to discontinuation of treatment in 7% of patients.

"We continue to be encouraged by the compelling safety profile and activity of tipifarnib as a monotherapy in this difficult-to-treat population of advanced head and neck cancer, supported by our Breakthrough Therapy Designation from the FDA," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Building on the results of the previous RUN-HN study, these data confirm that, in the proper biological context in which a target protein is obligately farnesylated, FTIs have potential to drive meaningful clinical benefit for patients. With these data in hand, we continue to evaluate in the ongoing KURRENT-HN study whether the combination of tipifarnib and alpelisib has potential to extend the clinical benefit observed in this study to a broader set of HNSCC patients."

"In addition," Dr. Wilson continued, "we believe these positive results from AIM-HN validate the therapeutic value of farnesyl transferase inhibition as we begin to execute on our clinical development plan for our next-generation FTI, KO-2806, which we will use to target other farnesylated targets such as RHEB and which we believe could become the preferred combination partner for a number of targeted therapies in multiple large solid tumor indications, including KRAS inhibitors in certain solid tumors and tyrosine kinase inhibitors in clear cell renal cell carcinoma."

About AIM-HN

AIM-HN is a multicenter, open-label, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC. Eligibility criteria include patients with recurrent or metastatic HRAS mutant HNSCC at any VAF level. The primary and key secondary endpoints of this trial include ORR and DoR in the high VAF population. The trial was designed to enroll at least 59 patients with HRAS mutant HNSCC who received prior platinum-based therapy and was closed to enrollment in November 2022. Further details regarding the trial are available at clinicaltrials.gov (NCT03719690).

About HNSCC

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, accounting for more than 500,000 new cases each year. Despite advances in immunotherapy, the prognosis for advanced HNSCC patients remains poor, with an estimated median overall survival of 13-15 months in patients when stratified by PD-L1 expression. Although the anti-epidermal growth factor receptor (EGFR) antibody, cetuximab, was approved more than a decade ago, development of biomarker-directed therapies in HNSCC has been stymied by the limited number of druggable targets in the genomic landscape and the challenge of managing drug refractory, recurrent/metastatic HNSCC.