On October 12, 2022 Mirati Therapeutics, Inc. (Nasdaq: MRTX), a clinical-stage targeted oncology company, and Aadi Bioscience, Inc. (Nasdaq: AADI), a commercial stage biopharmaceutical company focused on developing and commercializing precision therapies for genetically defined cancers with alterations in mTOR pathway genes, reported a clinical collaboration to evaluate the combination of adagrasib, a KRASG12C selective inhibitor, and nab-sirolimus, a small molecule mTOR inhibitor complexed with human albumin in KRAS G12C mutant non-small cell lung cancer (NSCLC) and other solid tumors (Press release, Mirati, OCT 12, 2022, View Source [SID1234621962]).

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The primary objective of this multi-center, single-arm, open-label Phase 1/2 trial is to determine the optimal dose and recommended Phase 2 dose for the combination of adagrasib and nab-sirolimus in patients with KRASG12C – mutant solid tumors. In addition, the study will investigate the safety, tolerability and efficacy of adagrasib and nab-sirolimus in combination in patients both with and without prior exposure to a KRASG12C inhibitor. The trial will build on preclinical data showing enhanced anti-tumor efficacy with the combination of adagrasib and nab-sirolimus relative to either agent alone.

"We are pleased to collaborate with Aadi on this clinical study of adagrasib and nab-sirolimus. Our collaborative preclinical work has demonstrated that combinatorial mTOR and KRAS inhibition addresses key bypass and feedback pathways associated with either drug target and also results in enhanced efficacy in tumor models harboring KRASG12C mutations. We believe the data from this trial may improve patient outcomes," said Charles Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "This clinical collaboration is an example of how Mirati is aggressively advancing the study of adagrasib both as a monotherapy and in rational combinations as part of our expanding development portfolio to benefit people living with difficult-to-treat cancers."

"KRAS and mTOR are closely linked and key pathways in oncogenesis and resistance to treatment. This collaboration builds on strong preclinical and mechanistic rationale supporting the combination of the two drugs to potentially provide greater benefit for patients with KRASG12C mutant NSCLC and other cancers," said Neil Desai, Ph.D., founder, president and chief executive officer, Aadi Bioscience, Inc. "We look forward to working closely with our Mirati counterparts to bring this treatment to those in need."

Under the terms of the collaboration agreement, Mirati will be responsible for sponsoring and operating the Phase 1/2 study, and jointly with Aadi, will oversee and share the cost of the study.

About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Studies of adagrasib have shown that the drug has a long half-life, extensive tissue distribution and is well tolerated. Adagrasib has also shown, in clinical trials, CNS penetrance and single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and other solid tumors with KRASG12C mutations. Adagrasib is being evaluated in several clinical trials in combination with other anti-cancer therapies with strong scientific rationale in patients with advanced solid tumors. Registration-enabling studies are ongoing in NSCLC and colorectal cancer. For more information visit Mirati.com/science.

About nab-sirolimus
Nab-sirolimus is a novel albumin-bound nanoparticle form of the mTOR inhibitor sirolimus and is currently being evaluated in a tumor-agnostic registration-directed trial in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. In November 2021, nab-sirolimus was approved by the U.S. Food and Drug Administration (FDA) as FYARRO for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

On October 12, 2022 Theriva Biologics, Inc. (NYSE American: TOVX), ("Theriva" or the "Company") reported that it is the new name of Synthetic Biologics, Inc. (NYSE American: SYN) (Press release, Synthetic Biologics, OCT 12, 2022, View Source,Theriva%20Biologics%2C%20Inc.&text=ROCKVILLE%2C%20Md.%2C%20Oct.,name%20of%20Synthetic%20Biologics%2C%20Inc. [SID1234621961]). The new name, logo and branding elements were introduced to better reflect Theriva’s position as a clinical-stage pharmaceutical company developing a novel oncolytic adenovirus (OV) platform to address devastating cancers with high unmet need. In addition, the Company announced its common stock is expected to begin trading on NYSE American under the new ticker symbol "TOVX" on Thursday, October 13, 2022.

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"The rebranding solidifies our strategic transformation and reflects our sharpened focus on advancing unique, oncolytic viruses optimized for IV administration," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "We continue to build on the incredible progress made to date and are diligently advancing our OV pipeline. This includes lead clinical-stage program VCN-01, designed to break down the tumor stroma, and preclinical-stage program VCN-11, leveraging our proprietary Albumin Shield Technology to protect systemically administered oncolytic viruses from the host immune system. These two differentiated programs are intended to improve the anti-tumor effect of the oncolytic virus, co-administered chemotherapies and/or immuno-oncology therapeutics. Together, VCN-01 and VCN-11 position Theriva at the forefronts of oncolytic virus development. We are excited about Theriva’s path towards strategic growth, renewed corporate strategy and remain on track to deliver on upcoming value-driving milestones."

The rebrand includes a new logo and corporate website that more accurately reflect the Company’s vision, mission and values. The unveiling of the rebranding is the culmination of an extensive effort to illustrate the Company’s potential to address devastating cancers with high unmet need through innovative therapeutic solutions with differentiated mechanisms of action.

Anticipated Milestones:

VCN-01

Initiation of VCN-01 dosing in an investigator sponsored study of brain tumors at the University of Leeds (H2 2022).
Initiation of a Phase 2 study of VCN-01 in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy in newly diagnosed metastatic PDAC patients (Q4 2022).
Clinical study initiation of VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma (H2 2023).
SYN-004

Initiation of the second cohort of the SYN-004 study in allo-HCT patients (H2 2022).

On October 12, 2022 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported that an abstract describing non-clinical and clinical data supporting the immune activating activity of ST101 has been selected for presentation at the upcoming SITC (Free SITC Whitepaper) 37th Annual Meeting, taking place November 8-12, 2022 in Boston, MA (Press release, Sapience Therapeutics, OCT 12, 2022, View Source [SID1234621960]).

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Poster Presentation Details:
Title: "ST101, a peptide antagonist of novel I/O target CEBPβ, reprograms MDSC polarization and decreases tumor-associated Tregs, suggesting an immune component to observed clinical responses"
Abstract Number: 1173
Location: Poster Hall C
Date/Time: Thursday, November 10, 2022 – Friday, November 11, 2022, 9am-9pm

The SITC (Free SITC Whitepaper) website indicates that all accepted abstracts will be published as a supplement in the Journal for ImmunoTherapy of Cancer (JITC), the society’s global, open access, peer-reviewed journal, which will be published on Nov. 7, 2022 at 8 a.m. EST.

About ST101
ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). ST101-101 is an open-label, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: Phase 1 dose escalation/regimen exploration and Phase 2 dose expansion. In the ongoing Phase 2 dose expansion, Sapience is actively enrolling patients with GBM, metastatic cutaneous melanoma, castration-resistant prostate cancer and locally advanced or metastatic hormone-receptor positive breast cancer. In the Phase 1 portion, ST101 demonstrated clinical proof-of-concept with a durable RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. In the ongoing Phase 2 dose expansion part of the study, ST101 has demonstrated clinical proof-of-concept with a mRANO-confirmed partial response in a patient with recurrent GBM and evidence of long-lasting stable disease in several additional patients.

ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as orphan designations from the FDA for advanced melanoma, glioma and AML, and from the European Commission for the treatment of glioma.

On October 12, 2022 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported that the first patient has been enrolled in the randomized controlled Part C of the ongoing DisTinGuish study to evaluate DKN-01, Leap’s anti-Dickkopf-1 (DKK1) antibody, in combination with tislelizumab, BeiGene’s anti-PD-1 antibody, and chemotherapy compared to a tislelizumab and chemotherapy control arm, in patients with gastric or gastroesophageal junction cancer (G/GEJ) (Press release, Leap Therapeutics, OCT 12, 2022, View Source [SID1234621959]).

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"We are excited to announce another important milestone for our DKN-01 clinical program in combination with our partner BeiGene’s tislelizumab, advancing this unique combination therapy into Part C of the DisTinGuish study," said Cynthia Sirard M.D., Chief Medical Officer of Leap Therapeutics. "The data to date from the DisTinGuish study show the DKN-01 plus tislelizumab combination therapy to be a compelling potential treatment for patients with G/GEJ cancer with response rates and survival outcomes that exceeded the benchmarks. This first randomized controlled study for DKN-01 will characterize the treatment effect in first-line patients, with a particular emphasis on those in the aggressive DKK1-high population."

The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. Part C of the DisTinGuish study will enroll approximately 160 first-line, HER2-negative patients. Patients will be randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy, compared to tislelizumab and SOC chemotherapy. The primary objective is progression-free survival (PFS) in DKK1-high patients. Secondary objectives of Part C include PFS in all patients regardless of DKK1 expression, as well as overall survival and objective response rate as measured by RECIST v1.1 in DKK1-high and all patients.

ABOUT DKN-01
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.

On October 12, 2022 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the publication of the abstract highlighting interim data from the ongoing phase 1/2 trial of the bispecific antibody MCLA-129 on the 34th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA Symposium) website (Press release, Merus, OCT 12, 2022, View Source [SID1234621958]). MCLA-129 is a fully human IgG1 Biclonics bispecific antibody that binds to EGFR and c-MET and is being investigated in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors. This phase 1/2 study has completed the dose escalation phase and is on-going in the dose expansion phase.

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The poster will be presented at the 34th ENA Symposium in Barcelona, Spain on Friday, October 28, 2022, 10:00-15:00 CET, and will be available online Wednesday, October 26, 2022. The poster presentation will include additional interim clinical data from this dose escalation cohort.

"We are encouraged by the promising initial clinical data for MCLA-129 presented in the abstract and are looking forward to providing additional clinical data from the dose escalation cohort in the poster presentation at the ENA Symposium," said Dr. Andrew Joe, Chief Medical Officer at Merus. "We also intend to share a MCLA-129 program update on our upcoming conference call."

The reported interim data in the abstract are from the phase 1/2 trial of MCLA-129 in patients with advanced NSCLC and other solid tumors.

Information and observations in the abstract include:

As of the May 8, 2022 cutoff date, 20 patients were treated with MCLA-129 across doses of 100, 300, 600, 1000, and 1500 mg every two weeks
Median age of patients was 65 years (range 43-79)
Tumor types enrolled included:
14 patients with EGFR mutant (mt) NSCLC (4 L858R, 8 Del19, 1 exon 20 insertion, 1 other)
2 patients with c-MET exon 14 mt NSCLC
1 patient with c-MET amplified gastric adenocarcinoma
1 patient with squamous cell esophageal cancer
2 patients with head and neck squamous cell carcinoma
13 patients were evaluable for response with preliminary signs of anti-tumor activity observed:
Two partial responses (one confirmed) in EGFR mt NSCLC
Four confirmed stable disease
Median duration of treatment was 8 weeks (range 3.4- 29.3) with 11 patients still on treatment at the cutoff date
Safety:
No dose limiting toxicity was observed and maximum tolerated dose was not reached
The most frequently reported adverse event (AE) was infusion related reaction (IRR)
18 of 20 pts (90%) reported IRR after first dose, all but one were mild or moderate (grade 1-2)
All but one infusion were completed on the same day
No treatment discontinuations due to AE
No interstitial lung disease was observed
Recommended initial phase 2 dose for expansion is 1500 mg every two weeks. The expansion cohorts are enrolling.
Dose-dependent depletion of soluble EGFR and c-MET was observed
In doses ranging from 600-1500 mg every two weeks, MCLA-129 demonstrated linear pharmacokinetics
Mean serum concentrations at 1500 mg every two weeks dose are modeled to be above that required for >95% target engagement of cell-bound EGFR and c-MET throughout the dosing period
Presentation Details:

Title: MCLA-129, a human anti-EGFR and anti-c-MET bispecific antibody, in patients with advanced NSCLC and other solid tumors: an ongoing phase 1/2 study
First author: Prof. Sai-Hong Ignatius Ou, Department of Medicine, Division of Hematology Oncology, University of California Irvine School of Medicine, US
Session: New Therapies in Immuno Oncology
Date: Friday, October 28, 2022
Time: 10:00-15:00 CET
Abstract #: 341
Poster #: PB121

The poster will be available at the start of the conference on October 26, 2022 and on-demand throughout the conference on the conference website. The poster will also be available on the Merus website contemporaneously.

Company Conference Call and Webcast Information

Merus will hold a conference call and webcast for investors on Wednesday, October 26, 2022 at 13:30 CET/7:30am ET to discuss the MCLA-129 initial clinical data and provide a program update. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time.

About MCLA-129
MCLA-129 is an antibody-dependent cellular cytotoxicity-enhanced Biclonics that is designed to inhibit the EGFR and c-MET signaling pathways in solid tumors. Preclinical data have shown that MCLA-129 can effectively treat TKI-resistant non-small cell lung cancer (NSCLC) in xenograft models of cancer. MCLA-129 is designed to have two complementary mechanisms of action: blocking growth and survival pathways to stop tumor expansion and recruitment and enhancement of immune effector cells to eliminate the tumor.