On July 16, 2024 Oncodesign Precision Medicine (OPM) (ISIN: FR001400CM63; Mnemonic: ALOPM), a biopharmaceutical company specializing in precision medicine for the treatment of resistant and metastatic cancers, reported positive results of phase 1 trial testing the drug candidate OPM-101, administered orally in single ascending doses (SAD) and multiple ascending doses (MAD), in healthy volunteers (HV) (Press release, Oncodesign, JUL 16, 2024, View Source [SID1234644902]).

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OPM-101 is an experimental, powerful and selective small molecule inhibitor of the RIPK2 kinase. OPM-101 is designed to modulate the pro-inflammatory signal transmission pathway of this kinase, which is responsible for the development of inflammatory diseases, and has the potential to treat diseases in the fields of IBD (Chronic Inflammatory Bowel Disease) and immuno-oncology. RIPK2 is a key protein in the regulation of immune responses and inflammatory processes. Recent research highlighted its potential as a therapeutic target, both in chronic inflammatory disorders and in several types of cancer.

This randomized, double-blind, placebo-controlled phase 1 study was designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of OPM-101 (EudraCT: 2022-003122-50) in 104 healthy volunteers (78 HV with OPM-101 and 26 with placebo):

In the SAD part of the trial, 72 HV (mean age = 34 years) received a single oral dose of placebo or 5, 20, 60, 150, 300, 600 or 1,000 mg of OPM-101, with one cohort dedicated to the high-fat meal effect and another to the gender effect.
In the MAD part of the trial, 32 HV (mean age = 36 years) received an oral dose of 75, 150 or 300 mg of OPM-101 or placebo twice daily for 14 consecutive days, including a cohort dedicated to the gender effect.
This phase 1 trial, which began in February 2023, was completed on schedule in June 2024.

The results of the SAD and MAD administrations in the clinical trial demonstrated that OPM-101 is well tolerated and significantly inhibits the RIPK2 pathway at doses as low as 60 mg single administration and 75 mg b.i.d. (bis in die – Twice daily). Target engagement kinetics and pharmacodynamic results showed a fast development of inhibitory effect, already observed 2 to 4 hours after the first administration, and inhibition maintained for 14 days of administration. The mean level of target engagement was 65% (75 mg b.i.d), 75% (150 mg b.i.d) and 85% (300 mg b.i.d) over the 14 days of treatment.

Safety evaluations (vital signs, blood tests, ECG, holters) were carried out regularly throughout the trial. The trial also collects secondary pharmacokinetic measures, including half-life assessments. Exploratory measures to assess OPM-101 target engagement were calculated by tracking changes from baseline in L18-MDP-stimulated TNFα production ex-vivo in whole blood samples.

The results of the MAD cohorts demonstrated maximum target engagement by OPM-101, demonstrated by a 90 to 100% reduction in TNFα production, leading to complete inhibition of stimulated production and a return to basal levels of TNFα, thus showing immunomodulation rather than total suppression of immunity as observed with other IBD treatments. This maximum engagement of the target was observed, depending on the dose, between 2 and 6 hours after the first administration of the treatment. Residual target engagement prior to the next dose was maintained over the 14 days of administration at mean levels of 65%, 75% and 85% with the 3 dose levels tested in MAD, respectively.

Involvement of the target in the MAD part of the study (inhibition of TNFα production induced by L18-MDP, in % of predose)

In the MAD part of the study, on Day 15, i.e., 24 hours after the last administration, 50%, 55% and 80% of target engagement were still observed in the three doses of MAD tested. At 48 hours after the last administration, target engagement levels gradually decreased as expected. These results demonstrate time- and dose-dependent target engagement. These proof-of-concept results for the immunomodulatory mechanism were obtained with oral administration of OPM-101 for 14 consecutive days, which was also generally well tolerated in all SAD and MAD cohorts.

No serious adverse event was reported. All treatment-emergent adverse events considered to be at least possibly related to the drug and the study were mild to moderate in both the SAD and MAD cohorts. Twelve healthy volunteers (15%) reported a total of 15 adverse events considered to be related to OPM-101. 80% of these events were mild and 20% moderate. There was no clinically significant change in safety-related laboratory tests reported during the treatment periods for all dose cohorts of OPM-101 included in the analysis, except for one volunteer who experienced a moderate (3N) increase in ALT (liver enzyme) during MAD, resulting in discontinuation of treatment after 12 days.

The pharmacokinetic results in the MAD part are consistent with those observed in the SAD part of the study. The main pharmacokinetic characteristics of OPM-101 are: fast absorption with a Tmax observed between 2-4h, a terminal half-life estimated at 12-13h, a steady state reached after 3-4 days and a dose-dependent exposure.

On the basis of the PK/PD correlation determined from the results of the SAD part of the study, we anticipate that a very significant target engagement (≥80%) can be achieved and maintained with a plasma concentration of OPM-101 remaining above 150 ng/mL in the interval between 2 treatment administrations. This threshold was achieved with the 2nd and 3rd dose levels in the MAD part of the study.

OPM plans to present additional results from the phase 1 cohorts at a future medical meeting in Q4 2024, subject to acceptance of the abstract by the United European Gastroenterology Week (UEGW) organizing committee.

Based on the results presented today, OPM plans to initiate enrolment in a phase 1b/2a clinical trial in the fourth quarter of 2024.

"We are very pleased with the progress and results of this clinical trial with OPM-101, which provided convincing results for all primary, secondary and exploratory endpoints included in this study," said Philippe Genne, Chief Executive Officer of OPM. "We are pleased to demonstrate the safety of our candidate and the strong PK/PD correlation that exists. High target engagement is demonstrated at tolerated doses of OPM-101 throughout the treatment period. The modulation of TNFα production ex vivo can be considered as a key biomarker of target engagement for future clinical trials. The clinical results reported today not only highlight the consistency with the immunomodulatory effect of OPM-101 observed in preclinical studies, but also validate OPM-101 as a safe and effective inhibitor of the RIPK2 pathway. We are currently in the process of identifying with our clinical experts the first clinical indication that we will explore in a phase 1b/2a study before the end of the year in order to provide a first clinical proof of concept in a patient population capable of generating significant added value for our asset".

"These results validate OPM-101 as a highly specific, effective and well-tolerated inhibitor of the RIPK2 immune pathway," added Jan Hoflack, Deputy CEO and Chief Scientific Officer of OPM. "The field related to this therapeutic approach is currently booming with new high quality preclinical and clinical scientific publications mentioning a potential role for an inhibitor like OPM-101 in multiple immuno-oncology indications, in addition to the already well-established rational for the treatment of IBD and other inflammatory diseases. Our team is currently working to validate the different therapeutic options available for OPM-101, with the aim of launching a proof-of-concept clinical trial in relevant patients rapidly and efficiently before the end of the year. The current idea of a safe and effective RIPK2 inhibitor like OPM-101 suggests significant potential in both IBD and immuno-oncology, two of today’s largest pharmaceutical markets with significant unmet needs".

On July 16, 2024 Scorpion Therapeutics, Inc. ("Scorpion"), a pioneering clinical-stage oncology company dedicated to transforming the lives of cancer patients by redefining the frontier of precision oncology, reported the closing of a $150 million Series C financing (Press release, Scorpion Therapeutics, JUL 16, 2024, View Source [SID1234644903]). The financing was co-led by Frazier Life Sciences and Lightspeed Venture Partners, and included additional new support from Willett Advisors and leading healthcare institutional investors, along with existing investors Omega Funds, Vida Ventures, Atlas Venture, Abingworth, Fidelity Management & Research Company, Boxer Capital, EcoR1 Capital, LLC, Surveyor Capital (a Citadel company), Invus, Wellington Management, Nextech Invest Ltd. (on behalf of one or more funds managed by it), OrbiMed, Logos Capital, Woodline Partners LP, and Casdin Capital, LLC. In connection with the financing, Shelley Chu, M.D., Ph.D., Partner at Lightspeed Venture Partners, will transition to an investor board member and Albert Cha, M.D., Ph.D., Managing Partner at Frazier Life Sciences, will join Scorpion’s board as an observer.

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"The robust demand for this capital raise is a testament to Scorpion’s continued clinical execution, the strength of our emerging clinical data, and the quality of our rapidly advancing pipeline," said Adam Friedman, M.D., Ph.D., Chief Executive Officer of Scorpion. "We are pleased to strengthen the Company’s financial position and expand Scorpion’s existing blue-chip investor syndicate with these additional leaders in life sciences who share our commitment to improving outcomes for people living with cancer by broadening the reach and impact of precision medicines."

"At Frazier Life Sciences, our goal is to invest in and develop transformational therapeutics companies. Scorpion continues to display an impressive track record of developing potentially best-in-class and first-in-class selective small molecule compounds for cancer," said Dr. Albert Cha. "With the combination of Scorpion’s clinical progress, advancing pipeline, validating partnerships and veteran leadership team, we believe the Company is well-positioned to rapidly develop therapeutics that will make a meaningful difference in patients’ lives."

"Lightspeed is pleased to support Scorpion through this important next phase of growth," said Dr. Shelley Chu. "The team has made remarkable progress since inception, and we believe Scorpion’s targeted approach may be able to overcome the selectivity challenges that plague existing treatment options, ultimately providing better outcomes to patients by offering improvements in both efficacy and safety. In particular, Scorpion’s mutant-selective PI3Kα inhibitor, STX-478, has the potential to become a best-in-class treatment for patients with PI3Kα-mutated breast cancer and other solid tumors, and we look forward to partnering with management to further explore STX-478 in mid-stage clinical trials."

Scorpion plans to use the proceeds from this financing to advance its pipeline of differentiated small molecule oncology programs, in particular, to expand clinical development of its allosteric, differentiated, mutant-selective PI3Kα inhibitor, STX-478. Further, the Company will continue to advance its clinical-stage EGFR inhibitor franchise, including STX-721 and STX-241, and its discovery pipeline of next-generation precision oncology therapies.

About STX-478

STX-478 was designed to improve outcomes in patients harboring PI3Kα mutations, one of the most prevalent drivers of cancer, occurring in over 166,000 patients per year with breast, gynecological and other solid tumors in the United States alone. In preclinical models, STX-478 demonstrated robust activity across a range of PI3Kα mutations while sparing wild-type PI3Kα inhibition in normal tissues; previous generations of non-selective PI3Kα inhibitors have limited patient benefit due to these on-target toxicities. Scorpion’s Phase 1/2 clinical trial is a multi-center, global, open-label study designed to evaluate the safety and tolerability of STX-478 in multiple ascending doses for patients with locally advanced or metastatic HR+/HER2- breast cancer and other solid tumors driven by PI3Kα mutations. The program entered the clinic in 2023 and has rapidly advanced, now in multiple expansion cohorts across a range of solid tumors and in breast cancer as monotherapy and in combinations with fulvestrant and CDK4/6 inhibitors. The Company remains on-track to disclose initial safety, pharmacokinetic and pharmacodynamic data, and preliminary efficacy data at a future academic conference. To learn more about the first-in-human trial of STX-478, please visit this page.

On July 16, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity", "the Company"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that it has entered into a supply agreement with TerraPower for Ac-225 for Clarity’s 225Ac-bisPSMA program (Press release, Clarity Pharmaceuticals, JUL 16, 2024, View Source [SID1234644867]).

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Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are very excited to explore the benefits of our proprietary optimised dual-targeted PSMA product in our first TAT program utilising TerraPower-supplied Ac-225. We have the right team to develop and later commercialise a best-in-class TAT product to complement the treatment paradigm, particularly in later-stage prostate cancer patients, and overcome the hurdles seen with other PSMA-based targeting agents.

"Manufacturing of Ac-225 poses a number of challenges at this time, including access for clinical studies, purity of isotope and scalability to meet requirements for a commercial launch. The Ac-225 from TerraPower fits into our strategy of developing sustainable, scalable and environmentally preferred solutions to radionuclide sourcing at a purity level appropriate for clinical practice and made directly in the United States. This avoids having to supply Ac-225 from Russia and use sources containing significant Ac-227 contamination, a radionuclide more radiotoxic than plutonium. A number of other isotope manufacturers are now developing potentially scalable commercial processes, including our existing partner for copper-67 supply, NorthStar Medical Isotopes LLC, and we will look to continue adding Ac-225 suppliers to our network. As such, with increasing focus on the Ac-225 supply chain, the probability of successfully developing and commercialising these treatments has grown from a supply perspective.

"The new beta-particle therapies, such as Cu-67 and Lu-177, with their favourable energy characteristics and path lengths, are revolutionising the radiopharmaceutical space because of their proven efficacy and excellent safety profiles compared to many other beta and alpha emitting isotopes. The small number of commercially available targeted radiopharmaceutical therapies all use beta emitting isotopes, and they represent the best opportunity to significantly change the treatment paradigm with the potential for much earlier stage treatments and in combination with standard of care treatments or immuno-oncology products. Novartis, the current leader in radiopharmaceuticals, has cornered much of the Lu-177 supply market, given the precarious supply chain of Lu-177 and reliance on a limited number of aging nuclear reactors, inhibiting new companies from entering this space1. Clarity’s unique proprietary position of having a cage that holds copper isotopes and exclusive supply of Cu-67, which is sourced from scalable electron accelerators as opposed to the small and aging fleet of nuclear reactors, means that Clarity is well positioned to drive a global shift in the treatment paradigm for cancer sufferers. As such, beta-particle therapy with Targeted Copper Theranostics (TCTs) remains Clarity’s key focus.

"Clarity’s bisPSMA program could be the game-changer in prostate cancer therapy given the increased uptake and retention in tumours enabled by the dual-targeting molecule and with impressive preclinical and clinical data generated to date. By combining our optimised bisPSMA with Ac-225, we have the opportunity to complement our beta-particle therapy product, 67Cu-SAR-bisPSMA. Developing both alpha- and beta-emitting therapy products for prostate cancer puts Clarity in a unique position to offer powerful treatment approaches to improve outcomes for these patients as using each product at different stages of the disease would provide more options to the patients.

"Our 225Ac-bisPSMA preclinical research program has been underway for some months with investigations to date focused on identifying a lead compound from a number of different analogues through measuring biodistribution, tumour uptake, radiolabelling efficiency and product stability as we move closer to clinical development with an optimised PSMA agent utilising Ac-225.

"By integrating TAT into our existing advanced TCT programs, Clarity is positioning itself to fundamentally transform the arsenal of treatments available for oncologists and their patients. This strategic move allows us to broaden our deep pipeline of clinical and pre-clinical assets and make significant progress towards our ultimate goal of better treating adults and children with cancer."

The Supply Agreement is effective July 2024. Supply under this agreement is expected to commence in November 2024, while supply before November 2024 will be carried out under the existing Limited Product Supply and Evaluation Agreement. The supply agreement is for an initial period of 2 years and can be extended under the terms of the contract. Cancellation provisions are at industry standard rates.

On July 16, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported that preliminary data from the monotherapy dose escalation portion of the ongoing Phase 1/2 clinical trial of CFT1946, a novel BiDAC degrader in mutant BRAF V600 solid tumors, will be presented as a mini oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 taking place September 13 – 17, 2024 in Barcelona, Spain (Press release, C4 Therapeutics, JUL 16, 2024, View Source [SID1234644887]).

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Details of the presentation are as follows:

Title: Preliminary Results from a Phase 1 Study of CFT1946, a Novel BIDAC Degrader in Mutant BRAF V600 Solid Tumors
Presentation Date and Time: Saturday, September 14, 2024, 2:45 – 2:50 CEST
Final Publication Number: 612MO
Session Category: Mini oral session
Session Title: Developmental therapeutics
Location: Oviedo Auditorium – Hall 3
Presenter: Maria Vieito, M.D., Msc (Barcelona, Spain, La Coruña)

On July 16, 2024 Tempus AI, Inc. (NASDAQ: TEM), a leader in artificial intelligence and precision medicine, reported that its multimodal immune profile score (IPS) algorithmic test is now available for research use only (RUO) (Press release, Tempus, JUL 16, 2024, View Source [SID1234644904]). IPS is the first offering of a larger immunotherapy-based portfolio being developed at Tempus to bring next-generation algorithmic diagnostics to the immuno-oncology space. Additionally, Tempus is collaborating with other partners, like Cleveland Clinic, to bring additional immunotherapy-focused algorithmic tests to this growing portfolio, leveraging clinical, laboratory, genomic, and transcriptomic data to identify patients that may respond to immunotherapy.

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Tempus’ IPS is a pan-cancer, laboratory developed test (LDT) that assesses a combination of immunotherapy-related biomarkers from prior DNA and RNA test results to calculate an IPS from 0-100 and a classification of either IPS-Low or IPS-High. IPS results can support patient stratification across pan-cancer cohorts to help inform who may or may not respond to immunotherapy. The IPS test is available today to life sciences partners for research use only, and is intended to be available as an add-on option for clinicians ordering Tempus’ xT and xR at the end of the year. Tempus is performing a retrospective, real-world study to evaluate the prognostic and the predictive utility of IPS in advanced pan-cancer patients treated with immune checkpoint inhibitors (ICI) and will be releasing data later this year.

In addition to developing and launching IPS, Tempus has licensed a machine-learning-based algorithmic test developed by Timothy A. Chan, MD, PhD, Cleveland Clinic. As described in Nature Biotechnology, the test demonstrates an ability to predict the efficacy of immune checkpoint blockade based on patient-specific biological, laboratory, genomic, and clinical factors, and adds to our expanding immunotherapy specific biomarker portfolio.

"Immune checkpoint inhibitors continue to have an incredible impact on patient outcomes, and we are excited to continue building a portfolio of AI-enabled diagnostics and tools to better equip clinicians in understanding which patients may benefit from these kinds of therapies," said Halla Nimeiri, MD, Chief Development Officer at Tempus. "The IPS test is our first multimodal algorithm to be introduced in the immunotherapy space, and we are excited to advance this field by providing critical insights that inform patient care."

"It’s a great pleasure to collaborate with Tempus on developing artificial intelligence powered models for better identification of patients who may respond to cancer immunotherapies," said Timothy A. Chan, MD, PhD, Department Chair of Immunotherapy and Precision Oncology and Professor of Medicine at Cleveland Clinic. "We look forward to working together with Tempus to bring multimodal immunotherapy response prediction assays to patients."

Tempus’ AI-enabled platform generates the type of rich multimodal data required to develop a novel class of predictive algorithms that can be introduced in the clinic to support personalized patient treatment selection. The IPS and Cleveland Clinic immune response tests joins a growing suite of algorithmic tests offered by Tempus, including Homologous Recombination Deficiency (HRD), Tumor Origin (TO), dihydropyrimidine dehydrogenase (DPYD), and PurISTSM. Each of these tests is designed to predict specific biological signals or clinical endpoints, ultimately supporting clinicians and life science partners as they seek to make more informed decisions for patients.

For more information on IPS, reach out to Tempus at tempus.com/contact-us.