On May 4, 2023 PharmaMar (MSE:PHM) reported the recruitment of the first patient in a new Phase I clinical trial for the treatment of patients with different types of solid tumors with its new molecule of marine origin: PM54 (Press release, PharmaMar, MAY 4, 2023, View Source [SID1234631045]).

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This is the first-in-human (FIH) clinical trial with this new compound that is being carried out in hospitals in Spain, other European countries and the United States. This clinical trial aims to find the recommended dose of the treatment.

This new molecule has been tested in the laboratory, both in cell cultures, in vitro, and in vivo. In both cases, PharmaMar’s new compound showed promising anti-tumor activity in a wide variety of tumor types. PM54 is the second PharmaMar compound to enter into the clinical development stage in the last few months after PM534, which FIH phase I trial was initiated in December 2022.

On May 4, 2023 Orna Therapeutics, a biotechnology company pioneering a new investigational class of engineered circular RNA (oRNA) therapies, reported two presentations at the Protein Engineering Summit (PEGS) taking place May 15-19 in Boston as well as a poster presentation at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting in Los Angeles May 16-20 (Press release, OrnaTherapeutics, MAY 4, 2023, View Source [SID1234631043]). Orna is presenting preclinical results for ORN-101, an in situ CAR program in development, as well as further details about its platform.

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"We are paving the way for advancements in RNA therapeutics that reach beyond infectious disease to treat cancer and genetic disorders," said Robert Mabry, PhD, Chief Scientific Officer at Orna. "Our ORN-101 program demonstrates the benefits of our platform’s ability to create a paradigm-changing treatment with the characteristics we believe matter most to patients, including a rapid timeline from diagnosis to treatment, strong expression and tumor-killing potency at low dose, and a regimen without the harsh chemotherapeutic lymphodepletion protocols typically required for standard engineered cell therapies."

Details for the presentations are as follows:

PEGS presentations

Title: Synthetic Circular RNA as a New Therapeutic Modality

Speaker & Chair: Nelson Chau, PhD, Senior Vice President, Platform

Session: Innovating RNA Therapeutics

Time: Tuesday May 16, 4:30pm ET

Title: In situ CAR Therapy Using oRNA

Speaker: Amy Becker, PhD, Director of Immunology

Session: Cellular Reprogramming, Increasing Specificity

Time: Thursday, May 18, 1:50pm ET

ASGCT poster

Title: In situ CAR Therapy Using oRNA Lipid Nanoparticles Regress Tumors in vivo

Speaker: Akinola Emmanuel, PhD, Principal Scientist

Board: 1119

Time: Thursday, May 18, 12-2pm PT

About ORN-101:

ORN-101, Orna’s lead program, is an in situ CAR therapy designed to modify a patient’s immune cells inside their body. Comprising an oRNA molecule packaged inside a proprietary lipid nanoparticls (LNP) formulation, this easily redosable format could avoid patient lymphodepletion and allow for reliable dose control, overcoming barriers of existing ex vivo CAR-T therapies without sacrificing efficacy. Preclinical data demonstrates tumor suppression and eradication in an animal model, suggesting the possibility that oRNA-LNP based cancer therapies could eventually overtake cell therapies.

On May 4, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported a business update and announced first quarter 2023 financial results (Press release, Oncternal Therapeutics, MAY 4, 2023, View Source [SID1234631042]).

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"Oncternal is intensely focused on advancing our cell therapy and androgen receptor (AR) inhibitor programs to reach significant clinical inflection points over the coming months. We are excited about the potential of ONCT-808, our ROR1-targeting CAR T, as it builds on the extensive clinical experience with zilovertamab, as well as with zilovertamab vedotin, an antibody drug conjugate, which has shown that ROR1 can be targeted without unwanted off-tumor, on-target activity. We are also enthusiastic about our novel and first-in-class dual-action AR inhibitor, ONCT-534, which demonstrated in preclinical studies that its unique mechanism of action may address significant unmet needs related to AR-resistance mechanisms in patients with metastatic castrate-resistant prostate cancer (mCRPC). We expect to initiate a Phase 1/2 study of ONCT-534 shortly after an IND submission in mid-2023, and to report initial clinical data in the first half of 2024, well within our expected cash runway period," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "Our decision to pause clinical development of zilovertamab with ibrutinib was a necessary step due to a major shift in the Bruton’s tyrosine kinase (BTK) inhibitor landscape, along with the announced plans by Abbvie to withdraw ibrutinib’s FDA accelerated approval in MCL. While we continue to actively explore options to develop zilovertamab through partnerships and collaborations, this decision allowed us to extend our expected cash runway into 2025 and support key clinical catalysts for our cell therapy and prostate cancer programs."

Recent Highlights

In January 2023, we obtained our first Institutional Review Board (IRB) approval for the Phase 1/2 study of ONCT-808 of our autologous ROR1 targeting CAR T for patients with aggressive B cell lymphoma (NCT05588440)
In March 2023, we concluded Investigational New Drug (IND)-enabling studies for ONCT-534, our novel dual-action androgen receptor inhibitor (DAARI) to support a Phase 1/2 clinical trial in patients with mCRPC who are resistant to androgen receptor (AR) inhibitor drugs such as enzalutamide and abiraterone
In April 2023, we announced that the Phase 3 and the Phase 1/2 studies of zilovertamab in combination with ibrutinib will be closed, based on the rapidly changing commercial landscape for BTK inhibitors
Expected Upcoming Milestones

ONCT-808, our autologous ROR1-targeted CAR T cell therapy
Initial clinical data available by the end of 2023
Additional clinical readouts in 2024
ONCT-534, our dual-action androgen receptor inhibitor
U.S. IND application submission in mid-2023
Phase 1/2 clinical study initiation in the second half of 2023
Initial clinical data available in the first half of 2024

First Quarter 2023 Financial Results

Our grant revenue was $0.2 million for the first quarter ended March 31, 2023. Our total operating expenses for the first quarter ended March 31, 2023 were $12.3 million, including $1.9 million in non-cash stock-based compensation expense. Research and development expenses for the quarter totaled $9.0 million, and general and administrative expenses for the quarter totaled $3.3 million. Net loss for the first quarter was $11.5 million, or a loss of $0.20 per share, basic and diluted. As of March 31, 2023, we had approximately 58.7 million shares of common stock outstanding, $54.3 million in cash, cash equivalents and short-term investments and no debt. We believe these funds will be sufficient to fund our operations into 2025.

On May 4, 2023 Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, reported financial results for the first quarter ended March 31, 2023, and highlighted recent Company progress (Press release, Omega Therapeutics, MAY 4, 2023, View Source [SID1234631041]).

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"During the first quarter we made progress across our clinical and preclinical programs in line with our broader strategic vision," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "We continue to enroll patients in the monotherapy arm of our Phase 1/2 MYCHELANGELO I study and remain on track to announce preliminary data this year. Additionally, we executed a key clinical supply agreement with Roche to evaluate the potential of our lead epigenomic controller, OTX-2002, in combination with atezolizumab, a leading anti-PD-L1 therapy, to explore the broader clinical potential of our new class of therapeutics. We expect that 2023 will be a pivotal year for Omega and we remain focused on advancing our novel approach to developing programmable epigenomic mRNA medicines in the service of patients."

Recent Corporate Highlights

•
Announced a Clinical Supply Agreement with Roche: In March 2023, the Company announced a clinical supply agreement with Roche to evaluate OTX-2002 in combination with atezolizumab, an anti-PD-L1 therapy, for the treatment of c-Myc (MYC)-driven hepatocellular carcinoma (HCC) as part of Omega’s Phase 1/2 MYCHELANGELO I clinical trial. Under the terms of this agreement, Roche will supply atezolizumab and Omega will evaluate the combination as part of the overall conduct of the trial.
•
Continued Enrollment into the MYCHELANGELO I Clinical Trial Evaluating OTX-2002: The Phase 1/2 study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of OTX-2002, the Company’s

lead Omega Epigenomic Controller (OEC) designed to downregulate MYC expression pre-transcriptionally, as a monotherapy (Part 1) and in combination with standard of care therapies (Part 2) in patients with relapsed or refractory HCC and other solid tumor types known for the association with the MYC oncogene. Trial enrollment continues to progress as planned at clinical sites across the U.S. and Asia. Preliminary data from the Phase 1 monotherapy dose escalation portion of the study, including initial safety, tolerability, pharmacologic and translational data, is expected in 2023.
•
Abstract Accepted for Poster Presentation at the Upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting: New preclinical data further validating Omega’s OEC platform will be shared in a poster presentation titled "Effect of MYC-targeting programmable epigenetic mRNA therapeutics on TME and immunotherapy responses" during the Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary session on June 5, 2023, from 8:00 a.m. to 11:00 a.m. CDT.
•
Advanced Preclinical Evaluation of OTX-2101 for NSCLC and Other OEC Development Candidates: Investigational New Drug (IND)-enabling studies for OTX-2101, the Company’s development candidate for the treatment of MYC-driven non-small cell lung cancer (NSCLC), continue to progress. Additional preclinical work is ongoing for other OEC development programs, including a CXCL 1-8-targeting OEC with potential in multiple indications including neutrophilic asthma, acute respiratory distress syndrome (including COVID-related), oncology, and dermatological and rheumatological indications, representing a potential franchise opportunity.

First Quarter 2023 Financial Results

As of March 31, 2023, the Company had cash, cash equivalents and marketable securities totaling $136.8 million, which includes the previously disclosed approximately $39.7 million in net proceeds received from a registered direct offering of common stock in February 2023. The Company anticipates that this balance will be sufficient to fund its operations into the second half of 2024.

Research and development (R&D) expenses for the first quarter of 2023 were $20.0 million, compared to $14.2 million for the first quarter of 2022. The $5.8 million increase in R&D expenses was primarily due to increases in personnel-related expenses, clinical development costs, and external manufacturing costs and study costs to support the advancement of our programs.

General and administrative expenses (G&A) for the first quarter of 2023 were $6.0 million, compared with $5.4 million for the first quarter of 2022. The $0.6 million increase in G&A expenses was primarily due to higher personnel-related expenses to support business growth.

Net loss for the first quarter of 2023 was $25.3 million, compared with $20.2 million for the first quarter of 2022. The increase in net loss was primarily due to increases in R&D expenses to support the Company’s programs and growth.

On May 4, 2023 NGM Biopharmaceuticals, Inc. (NGM Bio) (Nasdaq: NGM), a clinical-stage biotechnology company focused on discovering and developing transformative therapeutics for patients, reported financial results for the quarterly period ended March 31, 2023 and provided business highlights (Press release, NGM Biopharmaceuticals, MAY 4, 2023, View Source [SID1234631040]).

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"We are pleased with the results of the ALPINE 4 trial supporting the therapeutic potential of aldafermin in patients with advanced NASH. We continue to make progress on our corporate strategy with the initiation of Phase 2 expansion cohorts in our proof-of-concept trial of NGM707 and the extension of our expected cash runway. With these activities, we are optimizing our resource allocation strategy towards advancing our solid tumor oncology portfolio in the clinic, while our discovery engine continues to generate new product candidates," said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM Bio. "I would like to extend my sincere gratitude and thanks to NGM Bio’s departing staff impacted by our recent restructuring for their significant contributions and unwavering commitment to discovering and developing novel, life-changing medicines for people whose health and lives are disrupted by disease."

Key First Quarter and Recent Highlights

Corporate Updates

•Announced the appointment of Dan Kaplan, Ph.D. to Chief Scientific Officer. Dr Kaplan has been a member of NGM Bio’s Research and Development organization for fourteen years, most recently as Vice President, Immuno-oncology. Jin-Long Chen, Ph.D., who founded NGM Bio and served as Chief Scientific Officer and as a member of NGM Bio’s Board of Directors, resigned from NGM Bio effective April 4, 2023.
•Announced a restructuring resulting in a reduction of NGM Bio’s workforce by 75 people, or approximately 33% of the pre-restructuring headcount. NGM Bio expects to incur approximately $5.0 million in charges in connection with the restructuring, the majority to be incurred in the second quarter. The execution of the restructuring, including cash payments, will be substantially complete by the end of the second quarter.
Solid Tumor Oncology
•Initiated the first two Phase 2b cohorts in the Phase 1/2 trial evaluating NGM707 in combination with pembrolizumab.
•Continued enrollment in the Phase 1/1b trial evaluating NGM438, a LAIR1 antagonist antibody product candidate, as a monotherapy and in combination with pembrolizumab for the treatment of patients with advanced or metastatic solid tumors.

•Continued enrollment in the Phase 1/1b trial evaluating NGM831, an ILT3 antagonist antibody product candidate, as a monotherapy and in combination with pembrolizumab for the treatment of patients with advanced or metastatic solid tumors.
Phase 2b ALPINE 4 Trial Topline Results
•Today NGM Bio is reporting topline data from the Phase 2b ALPINE 4 trial of aldafermin in 160 patients with compensated cirrhosis due to NASH (liver fibrosis stage 4, or, F4). The 48-week trial assessed the efficacy, safety and tolerability of 1 mg and 3 mg doses of aldafermin compared to placebo1.
•The study met its primary endpoint with a statistically significant reduction in ELF score from baseline to week 48 in patients treated with 3 mg of aldafermin versus patients receiving placebo. Patients receiving 3 mg of aldafermin had a 0.5 point greater reduction in ELF at week 48 compared to patients receiving placebo (p-value = 0.0003). The ELF score is a reproducible, quantitative non-invasive liver prognostic test that evaluates liver fibrosis and correlates to liver-related outcomes.
•On the secondary endpoint of fibrosis improvement of ≥1 stage (for which the trial was not statistically powered) 21% (p-value=0.39) and 23% (p-value=0.36) of patients in the 1 mg and 3 mg cohorts, respectively, achieved fibrosis improvement versus 15% in the placebo cohort.
•Aldafermin was generally well tolerated with no treatment-related serious adverse events and a safety and tolerability profile generally consistent with prior trials of aldafermin, including higher levels of gastrointestinal events in patients treated with aldafermin as compared to patients treated with placebo.

"On behalf of the entire NGM Bio team, I’d like to thank the ALPINE 4 investigators and clinical trial staff, our employees who contributed to this effort and, most importantly, the patients who participated in the study," said Hsiao D. Lieu, M.D., Chief Medical Officer at NGM Bio. "We are encouraged that we continue to see evidence of the potential therapeutic activity of aldafermin, including on the ELF biomarker that has been correlated to patient outcomes, and we look forward to having conversations with potential partners to determine further development of the program."

First Quarter 2023 Financial Results

•NGM Bio reported a net loss of $47.6 million for the quarter ended March 31, 2023, compared to a net loss of $32.5 million for the same period in 2022.
•Related party revenue from our collaboration with Merck Sharp & Dohme LLC, or Merck, was $2.2 million for the quarter ended March 31, 2023, compared to $20.9 million for the same period in 2022. Our related party revenue from Merck decreased substantially after March 2022 and is expected to continue to decrease in 2023.
•R&D expenses were $40.9 million for the quarter ended March 31, 2023, compared to $42.8 million for the same period in 2022.
•General and administrative expenses were $11.6 million for the quarter ended March 31, 2023, compared to $10.7 million for the same period in 2022.

•Cash, cash equivalents and short-term marketable securities were $231.0 million as of March 31, 2023, compared to $271.5 million as of December 31, 2022. NGM Bio expects its cash, cash equivalents and marketable securities will be sufficient to fund its planned operations into the second quarter of 2025. NGM Bio has based this estimate on plans and assumptions that may prove to be insufficient or inaccurate (for example, with respect to anticipated costs, timing or success of certain activities), and the company could utilize its available financial resources sooner than it currently expects.