On October 23, 2024 Oncotelic Therapeutics, Inc (OTCQB:OTLC) reported its presentation at Precision in Drug Discovery & Preclinical Summit. Dr. Wen-Han Chang, Nanomedicine Sr. Manager, and Dr. Tara Zand, Research Scientist, presented Sapu Bio pipeline of TGFB2 therapeutics (Press release, Oncotelic, OCT 23, 2024, View Source [SID1234647345]). For additional information please go to: View Source

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Dr. Chang and Dr. Zand are experienced nanomedicine and precision drug development dedicated to finding the cure for pancreatic and brain cancers. View Source

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On October 23, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the company presented a poster highlighting certain best-in-class properties of ORIC-114, a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor, to treat EGFR exon 20 insertions and other atypical mutations at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics (Press release, ORIC Pharmaceuticals, OCT 23, 2024, View Source [SID1234647344]).

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"Preclinical data presented today underscore ORIC-114’s superior potency and selectively across EGFR mutational classes compared to other EGFR inhibitors," said Lori Friedman, PhD, chief scientific officer. "These results build on clinical findings that highlight ORIC-114’s potential best-in-class profile, showing notable systemic and CNS responses, along with a favorable safety profile, even in heavily pre-treated NSCLC patients. We are continuing to evaluate ORIC-114 in multiple Phase 1b expansion cohorts for NSCLC patients with EGFR exon 20, HER2 exon 20, and atypical EGFR mutations, with updated data expected in the first half of 2025."

Poster presentation details:

ORIC-114, a highly selective, brain penetrant EGFR and HER2 inhibitor, demonstrates best-in-class properties against exon 20 insertions and other atypical EGFR mutations

ORIC-114 previously demonstrated systemic and intracranial clinical responses in heavily pre-treated patients with EGFR and HER2 exon 20 insertion mutations. Key findings of this poster presentation:

Demonstrates regressions in all EGFR mutant in vivo models tested, including cell-derived xenografts, patient-derived xenografts and intracranial models that encompass exon 20 insertion and atypical mutant models. An in vivo model with complex atypical mutant EGFR dosed with ORIC-114 notably shows 100% tumor regressions and all tumors experienced a complete response.

In an expanded preclinical comparative analysis of exon 20 insertion, atypical PACC and other mutations, overall ORIC-114 is the most potent across EGFR mutational classes whilst displaying comparative wild-type selectivity in cell-based assays​, relative to firmonertinib, zipalertinib, lazertinib and BDTX-1535.

In head-to-head comparisons with firmonertinib, zipalertinib, lazertinib and BDTX-1535, ORIC-114 has superior kinome selectivity with no off-target kinase liabilities identified.

Shows complete molecular responses in ctDNA from patients with EGFR exon 20 insertion and PACC mutations from Phase 1 dose escalation study. Evidence of molecular responses observed across dose escalation cohorts supports broad therapeutic window for ORIC-114.

ORIC-114 is a promising therapeutic candidate with best-in-class potential for patients with non-small cell lung cancer harboring exon 20 insertions and atypical mutations in EGFR, including those presenting with active CNS metastases, and is being evaluated in a global clinical trial (NCT05315700).

About ORIC-114
ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, making it a promising therapeutic candidate to address the unmet medical need of having both meaningful systemic as well as CNS antitumor activity.

On October 23, 2024 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA" or the "Company"), a Phase 3 registration-stage immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, reported that TuHURA recently participated at the 2024 Maxim Healthcare Virtual Summit, Presented by Maxim Group LLC (Press release, TuHURA Biosciences, OCT 23, 2024, View Source [SID1234647343]).

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As part of the event, Dr. James Bianco, President and Chief Executive Officer of TuHURA participated in the Precision and Immune Oncology panel. To access the webcast replay, sign up to become anM-Vest member.

On October 23, 2024 Starget Pharma (Starget), a clinical stage biotechnology company developing precision peptide radioligand therapies, and Cancer Focus Fund, LP, a unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) to provide funding and clinical expertise to advance promising clinical therapies, reported a $5.1 million investment from Cancer Focus Fund to support a Phase 1b clinical trial of Starget’s lead theranostic, DOTA-PTR-58 (Press release, Starget Pharma, OCT 23, 2024, View Source [SID1234647342]). The trial will target tumors overexpressing somatostatin receptor type 3 (SSTR-3), including sarcomas, neuroendocrine tumors (NET), melanoma, and hepatocellular carcinomas. The trial will be conducted at MD Anderson and other centers and will begin enrolling patients in early 2025.

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Targeted theranostic radiotherapy combines diagnostic imaging with targeted treatment to provide personalized care for advanced metastatic cancers. Using patient data, theranostics precisely targets tumor cells, delivering localized radiotherapy that can either generate diagnostic images or directly destroy cancer cells. This approach offers greater precision and a wider therapeutic window than conventional radiation therapy.

"This investment validates the potential of our smart targeted radioligands to provide safer and more effective therapies for challenging cancers," said Sigal Kalmanson Cusnir, CEO of Starget Pharma. "Our Backbone Dynamics technology enables us to transform peptides into next-generation radiopharmaceuticals with enhanced properties. We look forward to collaborating with MD Anderson on this Phase 1b trial of DOTA-PTR-58, a first-in-class theranostic that has demonstrated both safety and tumor uptake in early studies. We believe our proprietary technology offers significant advantages over existing radioligand therapies, particularly for advanced cancer patients with limited options."

Starget’s Backbone Dynamics technology is an innovative peptide radioligand drug design platform that uses proprietary backbone cyclization to create molecules with enhanced stability, selectivity, and pharmacokinetics. The platform accelerates the design of new radioligand candidates, facilitating the rapid development of cancer therapies with enhanced efficacy and safety.

"Starget Pharma’s novel STR technology exemplifies the potential cancer breakthroughs we seek to support," said Ross Barrett, a founder and Managing Partner of Cancer Focus Fund. "Recent successes with peptide-based radioligands have begun to realize the promise of this approach, and Starget’s proprietary Backbone Dynamics technology further advances these gains by enhancing peptide diversity and optimizing candidate selection for a variety of difficult-to-treat cancers."

Jordi Rodón, MD, PhD, Associate Professor of Investigational Cancer Therapeutics at MD Anderson, will serve as Principal Investigator of the Phase 1b trial.

About DOTA-PTR-58 and SSTR-3
DOTA-PTR-58 is a first-in-class superagonist radioligand with sub-nanomolar affinity targeting selective somatostatin receptor type 3 (SSTR-3), a receptor highly expressed across multiple tumor types including sarcoma, melanoma, NET and hepatocellular carcinomas. Unlike the more commonly used target SSTR-2, SSTR-3 shows lower expression in normal tissues, offering a broader therapeutic window. DOTA-PTR-58 comprises a theranostic pair: Imaging with a Ga-68 isotope and therapy with a Lu-177 isotope. A follow-on program will include Imaging with a Ga-68 isotope and therapy with an Ac-225 isotope. The molecule demonstrates high in vivo tumor uptake and internalization, selectivity and significant antitumor activity.

On October 23, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported encouraging antitumor activity and safety/tolerability data for RMC-6236, its RAS(ON) multi-selective inhibitor, in patients with previously treated pancreatic ductal adenocarcinoma (PDAC) (Press release, Revolution Medicines, OCT 23, 2024, View Source [SID1234647341]). These updated results were presented during a late-breaking poster session at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, October 23-25, 2024.

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"The maturing data reported today continue to solidify the compelling progression-free survival and overall survival for patients with pancreatic cancer treated with RMC-6236, our oral RAS(ON) multi-selective inhibitor, in the Phase 1 study," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "These results support our ongoing Phase 3 registrational study, RASolute 302, and our belief that RMC-6236 monotherapy could potentially become an important therapeutic option for patients living with advanced or metastatic pancreatic cancer."

The RMC-6236-001 Phase 1/1b study is a multicenter, open-label, dose-escalation and dose-expansion study designed to evaluate RMC-6236 as monotherapy in patients with advanced solid tumors harboring RAS mutations or wild-type RAS. As of the July 23, 2024 data cutoff date, a total of 127 patients previously treated for PDAC were treated with RMC-6236 at doses ranging from 160 mg to 300 mg once daily (QD).

RMC-6236 appeared to be generally well tolerated at dose levels ranging from 160 mg to 300 mg QD and showed an overall safety profile consistent with previously reported results. No new safety signals were observed. The most common treatment-related adverse events (TRAEs) were rash and GI-related toxicities that were primarily Grade 1 or 2 in severity. The most common reported Grade ≥3 TRAEs were rash (8%), stomatitis (3%), and diarrhea (2%). TRAEs leading to dose modification occurred in 35% of patients with no treatment discontinuations due to TRAE. The average dose intensity across doses ranging from 160 mg to 300 mg was 92%.

RMC-6236 demonstrated durable antitumor activity as evidenced by updated progression-free survival (PFS) and overall survival (OS) at daily doses ranging from 160 mg to 300 mg, as described below. Patients with PDAC harboring a KRAS G12X mutation in the second-line (2L) setting achieved a median PFS of 8.5 months (95% confidence interval (CI), 5.3 – 11.7 months) and a median OS of 14.5 months (95% CI, 8.8 – not-estimable (NE)). Patients with PDAC harboring any RAS mutation in the 2L setting achieved a median PFS of 7.6 months (95% CI, 5.9 – 11.1 months) and a median OS of 14.5 months (95% CI, 8.8 – NE). Landmark OS for these patients at 6 months was 89% and 91% in patients with PDAC harboring a KRAS G12X mutation and patients with PDAC harboring any RAS mutation, respectively. The objective response rate for patients with tumors harboring KRAS G12X mutations was 29% in the 2L group and 22% in the third-line and beyond (3L+) group. The disease control rate was 91% and 89% in these patients, respectively.

"Pancreatic cancer remains one of the highest unmet needs in medicine. It is the most RAS-mutated of all major cancers with more than 90% of patients having tumors that harbor a RAS mutation," said Brian M. Wolpin, M.D., M.P.H., professor of medicine at Harvard Medical School, and director of the Gastrointestinal Cancer Center and Robert T. & Judith B. Hale Chair in Pancreatic Cancer at Dana-Farber Cancer Institute, principal investigator for the RMC-6236-001 study and lead author of the ENA presentation. "To see the level of clinical activity at doses with manageable tolerability demonstrated in this Phase 1 study is very exciting, providing much needed hope for patients with this difficult to treat cancer."

Investor Webcast
Revolution Medicines will host an investor webcast on Friday, October 25, 2024 at 6:00 p.m. Central European Standard Time to discuss the RMC-6236 and RMC-9805 monotherapy data in PDAC presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) ("Triple") meeting. To participate in the live webcast, participants may register in advance here. A live webcast of the call will be available on the Investors section of Revolution Medicines’ website at View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

About Pancreatic Cancer and Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that in 2024, approximately 60,000 people will be diagnosed with pancreatic cancer, and about 50,000 people will die from this aggressive disease.

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) and its variants, accounts for approximately 92% of all pancreatic cancer cases. Due to the lack of early symptoms and detection methods, approximately 80% of patients are diagnosed with PDAC at an advanced or metastatic stage. It is the most RAS-addicted of all major cancers, and more than 90% of patients have tumors that harbor RAS mutations. Metastatic PDAC remains one of the most common causes of cancer-related deaths in the U.S., with a five-year survival rate of approximately 3%.

About RMC-6236
RMC-6236 is an oral, direct RAS(ON) multi-selective inhibitor with the potential to help address a wide range of cancers driven by oncogenic RAS mutations. RMC-6236 suppresses RAS signaling by blocking the interaction of RAS(ON) with its downstream effectors. It does so across oncogenic RAS mutations G12X, G13X and Q61X, in major cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).