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 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 Hoth Therapeutics, Inc. (NASDAQ: HOTH), a patient-focused biopharmaceutical company, reported that it has received written approval from the GW University Hospital, UC Irvine and Northwell Health to proceed with its First-in-Human (FIH) Phase 2a clinical trial of HT-001 for the treatment of skin toxicities associated with Epidermal Growth Factor Receptor Inhibitors (EGFRi) (Press release, Hoth Therapeutics, JUL 16, 2024, View Source [SID1234644901]).

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"We are very pleased to have received approval from these three world class medical centers for our FIH clinical trial," said Hoth Therapeutics Chief Executive Officer, Robb Knie. "We are hopeful that this trial will demonstrate successful delivery of our lead therapeutic candidate HT-001 and bring hope to cancer patients suffering from skin toxicities associated with EGFRi treatments."

This Phase 2a dose- ranging study to investigate the efficacy, safety, and tolerability of topical HT-001 for the treatment of skin toxicities associated with EGFRi. More information can be found at clinicaltrials.gov.

On July 16, 2024 Genomics plc (Genomics), a healthcare company transforming health through the power of genomics reported a three-year extension of the company’s collaboration with Vertex Pharmaceuticals Incorporated (Vertex) (Nasdaq: VRTX) to use human genetics and machine learning to improve the discovery and development of new precision medicines (Press release, Vertex Pharmaceuticals, JUL 16, 2024, View Source [SID1234644900]). The partnership, which began in 2018, was previously extended in 2021. The collaboration will now run until 2026.

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The companies have been working together to support Vertex’s efforts to develop transformative medicines for serious diseases. To date, Genomics’ work has focused on using improved understanding of human genetics to pinpoint causal disease pathways and processes, and to identify novel targets in known and newly identified pathways.

As part of the extension, Genomics will expand the range of genomic insights it uses to support this work and expand the number of therapeutic areas under study. The partnership will now also explore using Genomics’ proprietary genetic tools to improve identification of patient populations and to de-risk the selection of biomarkers for measuring early readout of drug efficacy.

Mark Bunnage, Senior Vice President and Head of Global Research, Vertex:

"Vertex’s leading-edge discovery teams and R&D capabilities, and Genomics’ world class scientists, are at the forefront of using insights into human genetics to identify the most promising targets and advance them into medicines for patients. This collaboration has been valuable and productive, and we’re excited to continue and expand our transformative work right across the drug development pathway."

Professor Sir Peter Donnelly FRS, FMedSci, Founder and Chief Executive Officer, Genomics plc:

"We are proud to extend our partnership with Vertex once again. Our unique genomic data platform has meant that together, we have discovered novel genetically-validated targets with the potential to address diseases of high unmet medical need. Vertex is rightly recognized for its innovative pipeline and track record in developing treatments for serious diseases, which benefit the patients, families, and healthcare systems coping with these often life-threatening conditions. We are delighted to continue working with them to drive precision medicine approaches where treatments are tailored and delivered to those most likely to benefit."

On July 16, 2024 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported that updated data from the ARROS-1 Phase 1/2 clinical trial of zidesamtinib and ALKOVE-1 Phase 1/2 clinical trial of NVL-655, will be presented during two oral presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 taking place September 13-17, 2024, in Barcelona, Spain (Press release, Nuvalent, JUL 16, 2024, View Source [SID1234644899]).

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Details for the presentations are as follows:

Title: Phase 1/2 ALKOVE-1 study of NVL-655 in ALK-positive (ALK+) solid tumors
Presentation Number: 1253O
Session Category: Proffered paper session
Session Title: NSCLC metastatic
Presentation Date and Time: Saturday September 14, 2024, 9:40 – 9:50 CEST
Location: Barcelona Auditorium – Hall 2
Presenter: Alexander Drilon, M.D. (Memorial Sloan Kettering Cancer Center, New York, USA)

Title: Phase 1/2 ARROS-1 study of zidesamtinib (NVL-520) in ROS1 fusion-positive solid tumors
Presentation Number: 1256MO
Session Category: Mini oral session
Session Title: NSCLC metastatic
Presentation Date and Time: Saturday September 14, 2024, 10:30 – 10:35 CEST
Location: Santander Auditorium – Hall 5
Presenter: Benjamin Besse, M.D., Ph.D. (Institut Gustav Roussy, Villejuif, France)

Additionally, the company will present new preclinical data further characterizing the intracranial activity of zidesamtinib during a poster session. The title is:

Title: Profiling of Zidesamtinib and Other ROS1 Inhibitors in an Intracranial CD74-ROS1 G2032R Preclinical Model
Abstract Number: 4811
Presenter: Anupong Tangpeerachaikul (Nuvalent, Inc., Cambridge, Massachusetts, United States)

About zidesamtinib
Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, zidesamtinib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy. Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ROS1 tyrosine kinase inhibitors and orphan drug designation for ROS1-positive NSCLC. Zidesamtinib is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors.

About NVL-655
NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, NVL-655 is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. NVL-655 has received orphan drug designation for ALK-positive non-small cell lung cancer (NSCLC) and is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors.