On January 5, 2023 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), reported that management will provide an update on its pipeline and strategic priorities for 2023 during the Company’s presentation at the 41st Annual J.P. Morgan Healthcare Conference on January 12, 2023 at 9:00am PT (Press release, Terns Pharmaceuticals, JAN 5, 2023, View Source [SID1234625913]).

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"2022 was a transformative year for Terns as we made important steps forward in our commitment to provide better, new medicines to people battling diseases with significant unmet medical needs. Last year featured an evolution of our pipeline beyond NASH and obesity, as we advanced our oncology pipeline, which carries significant importance to me as an individual recently diagnosed with peritoneal cancer." said Sen Sundaram, chief executive officer of Terns Pharmaceuticals. "We expect 2023 to be an important year for Terns as we assess key inflection points for our clinical programs."

"Prior to our two recent financings, our cash runway supported three key clinical readouts from our three lead programs into 2025. In December 2022, we strengthened our third quarter cash balance sheet with $112 million in equity financing proceeds, resulting in an adjusted cash balance of $293 million.1 These resources are expected to now support operations into 2026, including multiple clinical trials for TERN-501, TERN-701 and/or TERN-601, with our resource allocation to be informed and driven by emerging data," said Mark Vignola, chief financial officer of Terns Pharmaceuticals. "This runway extension does not consider proceeds from potential collaborations in NASH or obesity, which would further solidify our balance sheet to invest more broadly across our development pipeline."

1 $187 million of cash, cash equivalents and marketable securities as of September 30, 2022, together with net offering proceeds of $106 million raised in December 2022

Anticipated 2023 Priorities and Key Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML)

Terns expects to initiate a clinical trial for TERN-701 in the United States in the second half of 2023, with potential top-line readouts from initial cohorts in 2024

The decision to initiate a U.S. trial, as well its design, will be informed by data from the ongoing Phase 1 trial conducted by our partner Hansoh in China. The Hansoh trial is a dose-escalation and dose-expansion trial (NCT05367700) evaluating the tolerability, efficacy, and pharmacokinetics of TERN-701 (HS-10382) in approximately 100 patients with CML

Terns expects to publish preclinical data demonstrating TERN-701’s potential in CML and plans to prioritize ongoing publication and presentation of additional supportive data

Due to innovation-limiting price controls for orphan drugs approved for more than one indication that was introduced in the Inflation Reduction Act of 2022 (IRA), Terns does not plan to pursue regulatory approval of TERN-701 for Ph+ acute lymphocytic leukemia (ALL) in the United States, but may pursue approval in countries outside of the United States. Terns continues to evaluate the impact of the IRA across its entire clinical program
"As a peritoneal cancer patient, I have benefitted from treatment with older cancer drugs being studied for new purposes. As such, it pains me to have to forsake my fellow cancer fighters in the United States because of economic policies that stifle medical innovation. I worry that many treatments, such as those that have temporarily extended my own life, could also be abandoned in the United States, and may only wind up being approved in other countries outside the United States," added Mr. Sundaram.

TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist for NASH

The Phase 2a DUET trial (NCT05415722), evaluating TERN-501 as a monotherapy and in combination with TERN-101, is on track to complete enrollment in the first quarter of 2023 with top-line data now expected in the third quarter of 2023

Primary endpoint is the relative change from baseline in liver fat content as measured by MRI protein density fat fraction (MRI-PDFF) at Week 12 for TERN-501 monotherapy compared with placebo

Secondary endpoints include assessment of safety and tolerability, pharmacokinetics, changes in MRI-PDFF and MRI corrected T1 (cT1)

DUET is the first trial assessing a THR-β agonist as monotherapy and in combination with an FXR agonist in people with NASH

TERN-501 is a THR-β agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β compared to other THR-β agonists in development

TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

Terns’ lead GLP-1 receptor agonist program remains on track with the goal of initiating a Phase 1 first-in-human clinical trial in obesity in the second half of 2023 with top-line data expected in 2024

The Company expects to publish preclinical data demonstrating TERN-601’s potential in obesity and plans to prioritize ongoing publication and presentation of additional supportive data

Pre-clinical and Discovery Programs

Terns is conducting pre-clinical in vivo studies evaluating TERN-201, a vascular adhesion protein-1 (VAP-1) inhibitor, co-administered with immune checkpoint inhibitors (e.g., anti-PD1 and anti-CTLA4 antibodies) for solid tumors

Discovery efforts are ongoing for the TERN-800 series of small molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) modulators for obesity, which have the potential for combination with GLP-1 receptor agonists, such as TERN-601
A live audio webcast of the Company’s J.P. Morgan Healthcare Conference presentation will be available on the investor relations page of the Terns Pharmaceuticals website at View Source A replay of the webcast will be archived on Terns’ website for 30 days following the presentation. yhip-

On January 5, 2023 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that the first patient has been dosed in its Phase 1/2 clinical study investigating SRF114, a potential best-in-class, fully human, afucosylated anti-CCR8 antibody, as a monotherapy in patients with advanced solid tumors (Press release, Surface Oncology, JAN 5, 2023, View Source [SID1234625911]).

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"Helping patients fight cancer by depleting intra-tumoral regulatory T cells (Tregs) has been a key goal of many immunotherapy strategies for quite some time. We believe by targeting CCR8, SRF114 is well suited to explore the promise of this approach," said Alison O’Neill, M.D., chief medical officer of Surface Oncology. "We selected our SRF114 antibody based on its highly specific binding properties to human CCR8 exclusively, which we believe positions it as a potential best-in-class anti-CCR8 antibody for the treatment of advanced solid tumors."

The Phase 1/2 trial is an open-label, first-in-human, dose-escalation and expansion study of SRF114 as a monotherapy in patients with advanced solid tumors that will be conducted in two parts. Part A, the monotherapy dose-escalation portion of the study, will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of SRF114 in patients with advanced solid tumors. Once Part A is completed, Part B will evaluate SRF114 in up to 40 patients with head and neck squamous cell carcinoma (HNSCC) as a monotherapy. Surface expects to provide initial clinical data in 2024.

About SRF114

SRF114 is a fully human, afucosylated anti-CCR8 antibody designed to preferentially deplete CCR8+ Treg cells within the tumor microenvironment. In pre-clinical studies, Surface Oncology has shown that SRF114 induces antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) pathways to deplete intratumoral Treg cells. In addition, SRF114 reduced tumor growth in murine models. These findings support the advancement of SRF114 as a therapeutic candidate that holds the potential to drive anti-tumor immunity in patients.

On January 5, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer, reported a clinical supply agreement with Regeneron for its anti-PD1 therapy Libtayo (cemiplimab) (Press release, Sensei Biotherapeutics, JAN 5, 2023, View Source [SID1234625910]). The supply agreement supports the evaluation of SNS-101, a conditionally active VISTA-blocking antibody, in combination with Libtayo in a Phase 1/2 trial in solid tumors. Sensei is on track to submit an Investigational New Drug application for SNS-101 in or before April 2023 and the trial is expected to commence in 2023 pending regulatory clearance.

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"We are excited for the opportunity to work with Regeneron on our planned clinical trial of SNS-101, which has demonstrated strong anti-tumor activity in combination with PD-1 inhibition in preclinical studies. We look forward to exploring the potential of SNS-101 to inhibit tumor growth across a range of indications," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "We have built a robust preclinical data package supporting the biological rationale for our pH-sensitive approach, which we believe offers both safety and efficacy advantages over pH-independent VISTA antibodies, including the potential to avoid poor pharmacokinetics from target-mediated drug disposition and lower the risk of cytokine release syndrome."

Under the terms of the agreement, Sensei will sponsor and fund the planned clinical trial and Regeneron will provide Libtayo. Sensei will maintain global development and commercial rights to SNS-101. Regeneron develops and commercializes Libtayo globally.

SNS-101 is currently under preclinical development, and the safety and efficacy of SNS-101 or its administration with Libtayo have not been reviewed by any regulatory authorities.

On January 5, 2023 QIAGEN (NYSE:QGEN; Frankfurt Prime Standard: QIA) reported an exclusive strategic partnership with California-based population genomics leader Helix to advance companion diagnostics for hereditary diseases (Press release, Qiagen, JAN 5, 2023, View Source [SID1234625909]).

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As the development of precision medicines accelerates, so does the need for companion diagnostics devices and tests detecting clinically relevant genetic abnormalities. These diagnostics help guide clinical decision-making by identifying patients most likely to benefit – or be at increased risk – from a particular therapeutic product. Principally used in oncology to date, companion diagnostics that employ whole exome sequencing are widely believed to have great potential in hereditary disease areas such as cardiovascular, metabolic, neuro-degenerative, and auto-immune diseases.

Under the agreement announced today, QIAGEN will be the exclusive marketing and contracting partner in the U.S. for Helix’s companion diagnostic services. The partnership will leverage the Helix Laboratory Platform, which was granted the first-ever U.S. Food & Drug Administration de novo class II authorization for a whole exome sequencing platform. This brings a new innovative solution to biopharmaceutical customers in support of hereditary disease therapies, complementing solutions both companies already provide such as Helix’s population genomics programs and QIAGEN’s diagnostic expertise, QIAseq Human Exome Kits and global reach supporting research initiatives outside the U.S.

A pioneer in precision medicine, QIAGEN has more than 30 master collaboration agreements with global pharmaceutical and biotechnology companies to develop and commercialize companion diagnostic tests for their drug candidates. QIAGEN’s companion diagnostic offerings encompass technologies from next-generation sequencing (NGS) to polymerase chain reaction (PCR) and digital PCR (dPCR), sample types from liquid biopsy to tissue, and disease areas from cancer to Parkinson’s – including 11 FDA-approved PCR based companion diagnostics and a collaboration with Neuron23 announced in September 2022 to develop an NGS-based companion diagnostic for a novel Parkinson’s disease drug.

"This partnership represents another step toward bringing the power of companion diagnostics to hereditary diseases by powering Helix’s leading products with QIAGEN’s extensive pharma and biopharma relationships, NGS capabilities, and global regulatory expertise," said Thierry Bernard, Chief Executive Officer of QIAGEN. "Access to a genomic database can help researchers find patients with particular biomarker signatures almost instantaneously, making trial recruitment a matter of months instead of years."

"Helix’s technology and regulatory capabilities coupled with QIAGEN’s well-established worldwide companion diagnostic development capabilities results in a powerful partnership that will allow us to expand critical access to genomic testing for both patients and providers working daily to fight life-threatening conditions," said Helix CEO and Co-Founder, James Lu, MD, PhD. "QIAGEN’s mission to fill the clinical gap for patient access and provide technology platform options to address the needs of physicians to target treatment with genomic medicine is well in line with our mission."

Helix has built an end-to-end platform that enables health systems, life sciences companies, and payers to advance genomic research and accelerate the integration of genomic data into clinical care. Helix has partnered with leading health systems to enable population genomics programs of at least 100,000 patients each across the U.S. These programs dramatically accelerate patient identification and recruitment for clinical trials in hereditary diseases such as Parkinson’s, cardiovascular or inflammatory disease like non-alcoholic steatohepatitis (NASH), power real-world data (RWD) or real-world evidence (RWE) services and insights, and bring deep genetic expertise and methodologies to examine sub-cohorts within both drug discovery and a clinical trial.

On January 5, 2023 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized immunotherapies, reported that it has entered into a clinical trial collaboration and supply agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA), to evaluate Nouscom’s wholly-owned lead candidate, NOUS-209, in combination with
MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) versus KEYTRUDA alone in randomized Phase 2 trials in patients with Mismatch Repair/Microsatellite Instable High (dMMR/MSI-H) Metastatic Colorectal Cancer (CRC) (Press release, NousCom, JAN 5, 2023, View Source;utm_medium=rss&utm_campaign=nouscom-announces-clinical-trial-collaboration-and-supply-agreement-with-msd-to-evaluate-nous-209-in-combination-with-keytruda-pembrolizumab-in-a-phase-2-randomized-trials-in-dmmr-msi-high-met [SID1234625906]). NOUS-209 is an off-the-shelf immunotherapy targeting 209 specific, shared neoantigens found in dMMR/MSI-H unresectable or metastatic gastric, colorectal and gastro-esophageal junction tumors.

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The Phase 2 study includes two cohorts in dMMR/MSI-H unresectable and metastatic CRC assessing the efficacy and safety of NOUS-209 in combination with pembrolizumab at multiple active sites across Europe and the US (NCT04041310).

1. A randomized cohort enrolling patients who are eligible for first line treatment, randomized

2:1 to NOUS-209 plus pembrolizumab versus pembrolizumab alone;

2. A single arm cohort enrolling patients who have stopped responding to previous anti-PD1 treatment.

Dr Marina Udier, Chief Executive Officer of Nouscom, added: "We are thrilled to collaborate with MSD, a global leader in immuno-oncology, and to work with their highly experienced and talented clinical development team, allowing us to accelerate the ongoing US and EU Phase 2 trial with NOUS-209. Based on our published and presented Phase 1 clinical data1,2 we see great potential of this combination approach in addressing the unmet medical need in these patients.
We look forward to presenting preliminary data in 2023."

Under the terms of the agreement, MSD will supply KEYTRUDA. Nouscom retains all worldwide commercial rights to NOUS-209.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

References

1. ASCO (Free ASCO Whitepaper) Presentation: First clinical and immunogenicity results including all subjects enrolled in a phase I study of NOUS-209, an off-the-shelf immunotherapy, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability (dMMR), Professor Marwan G. Fakih, M.D.

2. A.M. D’Alise et al. Adenoviral Based-Vaccine Promotes Neoantigen Specific CD8+ T Cell Stemness And Tumor Rejection, Science Translational Medicine; 14, 657, 2022

About NOUS-209

NOUS-209 is an off-the-shelf cancer immunotherapy for Microsatellite Instable High (MSI-H) tumors. MSI-H tumors are characterized by a defective DNA mismatch repair system, which generates highly immunogenic neoantigens called frame shift peptides (FSP) that are not present in healthy tissue.

NOUS-209 encodes for 209 shared FSP neoantigens, selected by Nouscom’s proprietary GENESIS (GE(netic)NE(oantigen)S(election)I(n)S(ilico)) algorithm. In published prospective validation studies, approximately 50 of the 209 neoantigens are expressed in any one patient’s tumor. These FSPs are cloned into Nouscom’s heterologous prime / boost viral vector platform of a Great Ape Adenoviral (GAd) and Modified Vaccinia Ankara (MVA) and potently generate FSP neoantigen specific CD8+ T cells, which have been shown to successfully infiltrate tumor microenvironments to exert anti-tumor activity.

NOUS-209 is being investigated in multi-center EU and US Phase 2 randomized clinical trials in patients with dMMR/MSI-H unresectable and metastatic colorectal cancer (CRC) (NCT04041310) in combination with checkpoint inhibitors (CPI) versus CPI alone and in patients who have stopped responding to previous anti-PD1 and other approved CPI therapies.