On January 11, 2022 Lucence, a precision oncology company using liquid biopsy to bring clarity to cancer care, reported the availability of an expanded version of its flagship LiquidHALLMARK liquid biopsy assay that includes both cell-free DNA (cfDNA) and cell-free RNA (cfRNA) profiling (Press release, Lucence Diagnostics, JAN 11, 2022, View Source [SID1234598596]). LiquidHALLMARK cfDNA and cfRNA is currently available to US oncologists as a laboratory developed test and is being utilized by physicians at NCI-designated centers across the country.

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Most liquid biopsies available today interrogate cell-free DNA (cfDNA) as the sole analyte. However, for the detection of certain fusions, including those that have long intronic regions such as NTRK and NRG1, incorporation of RNA sequencing can be advantageous. Gene fusions like NTRK and NRG1 have emerged as clinically significant and actionable biomarkers that can help guide physicians to matched targeted therapies. Ryma Benayed and co-authors demonstrated that adding targeted RNA sequencing to DNA sequencing to tissue testing could obtain an additional 14% yield of clinically actionable alterations.

An internal validation study conducted by Lucence also supports this approach. Out of 112 non-small cell lung cancer (NSCLC) samples, 29 fusions were detected with a combined cfDNA and cfRNA approach in plasma, compared with 20 fusions from cfDNA alone.

"Including cfRNA in a liquid biopsy assay has a significant impact on the detection of clinically relevant fusions. This solves a major known limitation of cfDNA-only assays, which have more limited fusion detection capabilities. For example, NTRK fusions which have corresponding approved TRK inhibitors, and NRG fusions which have multiple emerging therapies, are best detected by a combination of both DNA and RNA testing. This is an exciting opportunity to help more cancer patients through broader and more accurate targeting," said Professor Gilberto Lopes, Chief of Medical Oncology at Sylvester Cancer Center at the University of Miami.

"Lucence’s experience using AmpliMark for SARS-CoV-2 as part of the fight against the COVID-19 pandemic gave us the experience with RNA to be able to expand our assay to detect fusions in cancer. It’s a great example of how R&D developed to fight COVID can now be used for ultrasensitive cancer diagnostics," said Dr. Min-Han Tan, MBBS, PhD, Founding CEO and Medical Director of Lucence.

Lucence’s LiquidHALLMARK cfDNA and cfRNA panel combines cfRNA profiling of 27 actionable and emerging fusions with cfDNA profiling of mutations in 80 genes, fusions in 10 genes, and somatic variants in 15 cancer types. LiquidHALLMARK is powered by AmpliMark, the Company’s proprietary amplicon-based sequencing technology, which uses a unique molecular barcode and error-correction technology to ensure test sensitivity across multiple mutation types for single nucleotide variants and fusion genes.

On January 11, 2022 Aligos Therapeutics, Inc. (Nasdaq: ALGS) a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, reported that it has expanded its ongoing collaboration agreement with Merck to discover and develop oligonucleotide therapies for non-alcoholic steatohepatitis (NASH) (Press release, Aligos Therapeutics, JAN 11, 2022, View Source [SID1234598595]).

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"We believe that one of our strengths as a company is our technical know-how in several areas of oligonucleotide research and development," said Lawrence Blatt, Ph.D., MBA, Chairman and Chief Executive Officer of Aligos. "We are pleased to broaden our collaboration where we may be able to contribute to creating effective, targeted therapies for NASH together with Merck."

Under the original agreement, Merck and Aligos committed to applying Aligos’ oligonucleotide platform technology to discover, research, optimize and develop oligonucleotides directed against a certain undisclosed non-alcoholic steatohepatitis (NASH) target and up to one additional target of interest in the cardiometabolic/fibrosis space. That agreement has now been expanded to include the in-license by Merck of an early-stage program with respect to a second undisclosed NASH target on which Aligos has previously been working independently and separately from Merck. In addition, under this expanded arrangement, Merck has the ability of adding an additional third target of interest in the cardiometabolic/fibrosis space to the collaboration.

"We are encouraged by the progress made to date in our ongoing collaboration with Aligos and look forward to applying Aligos’ technology towards a second target moving forward," said Dr. Ajay Chawla, Vice President, Cardiometabolic Disease Discovery, Merck Research Laboratories.

Under the expanded agreement, Aligos will receive a payment from Merck for the in-license of the program directed at a second undisclosed NASH target. Additionally, Aligos will receive an additional payment upon designation of a third target for the collaboration. With respect to each target in the collaboration, Aligos will be eligible to receive up to ~$460M in development and commercialization milestones as well as tiered royalties on net sales. Aligos is primarily responsible for designing, synthesizing and evaluating the oligonucleotide candidates and delivering optimized lead molecules. Thereafter, Merck is responsible for subsequent research, clinical development and commercialization.

On January 11, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported the company has entered into a strategic research collaboration with Pepscan Therapeutics B.V. (Pepscan) to discover novel, peptide-based radiopharmaceuticals for the treatment of various solid tumors (Press release, Fusion Pharmaceuticals, JAN 11, 2022, View Source [SID1234598593]).

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"Fusion’s internal research and develop capabilities combined with expertise in radiopharmaceuticals allow us to create novel targeted alpha therapies (TATs) using a variety of classes of targeting molecules, including antibodies, small molecules and peptides – all of which have been used successfully in radiopharmaceutical development," said Fusion Chief Executive Officer John Valliant, Ph.D. "We are pleased to work with Pepscan who has a proprietary platform for peptide discovery that will enable us to create novel, peptide-based targeted alpha therapies (TATs), further augementing our pipeline of radiopharmaceuticals."

Under the agreement, Fusion has global rights to develop and commercialize any peptides discovered under the collaboration.

On January 11, 2022 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported a pipeline milestone update on its TriTAC development programs (Press release, Harpoon Therapeutics, JAN 11, 2022, View Source [SID1234598592]).

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"We are excited to begin 2022 with a catalyst rich year that will be driven by our multiple TriTAC clinical programs, including advancing our HPN217 program into the next phase of development," stated Julie Eastland, President and CEO, Harpoon Therapeutics. "We also expect to submit our first IND for HPN601, targeting EpCAM, from our ProTriTAC technology platform as well as advance an additional preclinical candidate into IND enabling studies as we continue to build out our future clinical pipeline."

Anticipated 2022 Milestones

TriTAC Clinical Programs

HPN328 – Continue dose escalation to determine RP2D by year-end 2022

HPN217 – Select the RP2D and initiate dose expansion cohort during the first half of 2022

HPN536 – Complete dose escalation by year-end 2022

HPN424 – Complete dose escalation during the second half of 2022
Platform Technologies and Next Clinical Candidate

HPN601 – IND submission by year-end 2022

Platform technologies – Advance a clinical candidate into IND enabling studies during the second half of 2022
Corporate Update Events

Harpoon will host an R&D Day during the first half of 2022

On January 11, 2022 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported that key strategic priorities and upcoming catalysts to support its lead compound VS-6766 in 2022 (Press release, Verastem, JAN 11, 2022, View Source [SID1234598591]). VS-6766 is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF, potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. VS-6766 is currently in late-stage development.

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"Building on the Breakthrough Therapy designation for VS-6766 with defactinib in recurrent low-grade serous ovarian cancer, the significant progress of our RAMP program in both low-grade serous ovarian cancer and KRAS G12V-mutant non-small cell lung cancer, our clinical collaborations in KRAS G12C-mutant non-small cell lung cancer as well as our ongoing investigator-initiated trials program, we expect to see tremendous progress on behalf of patients in 2022," said Brian Stuglik, CEO of Verastem Oncology. "We plan to efficiently advance our development strategy, report multiple data readouts and further highlight the differentiated potential of VS-6766 across tumor types and mutations."

2022 Strategic Priorities

Gynecologic Oncology Program

Fully enroll Part B of the RAMP 201 trial (LGSOC VS-6766 +/- defactinib).
Expand development program into other RAS pathway-driven gynecologic cancers.
Non-Small Cell Lung Cancer (NSCLC) Program

Select regimen for Part B of the RAMP 202 trial (KRAS G12V NSCLC VS-6766 +/- defactinib).
Initiate and complete dose-finding portions of RAMP 203 (KRAS G12C NSCLC VS-6766 + LUMAKRASTM (sotorasib)) and RAMP 204 (KRAS G12C NSCLC VS-6766 + adagrasib) combination trials.
Provide signal read-out of investigator-sponsored trial of VS-6766 and everolimus in KRAS- mutant NSCLC.
Other Programs

Expand investigator-initiated trial program to include signal-finding studies in other tumor types, including melanoma, breast and colorectal cancers.
Expand clinical combinations with VS-6766.
Anticipated 2022 Development Milestones and Catalysts

1Q-2022

Having completed target enrollment (n=64) in the selection phase (Part A) of the Phase 2 RAMP 201 trial (LGSOC VS-6766 +/- defactinib), the enrollment phase (Part B) is now ongoing with both treatment arms currently advancing.
Complete enrollment in the selection phase (Part A) of the Phase 2 RAMP 202 trial (KRAS G12V NSCLC VS-6766 +/- defactinib).
Initiate RAMP 203 trial (KRAS G12C NSCLC VS-6766 + LUMAKRASTM (sotorasib)) with Amgen.
Q2-2022

Report topline results from Part A of the RAMP 201 trial (LGSOC VS-6766 +/- defactinib), following discussions with regulatory authorities.
Initiate RAMP 204 trial (KRAS G12C VS-6766 + adagrasib) with Mirati.
Present topline results of investigator-initiated trial of VS-6766 and everolimus in KRAS-mutant NSCLC.
Present investigator-initiated FRAME LGSOC translational data.
2H-2022

Complete enrollment in the RAMP 201 trial (LGSOC VS-6766 +/- defactinib).
Report topline results from RAMP 202 trial (KRAS G12V NSCLC VS-6766 +/- defactinib) and initiate the expansion phase (Part B), following discussions with regulatory authorities.
Report initial readout of the RAMP 203 trial (KRAS G12C NSCLC VS-6766 + LUMAKRASTM (sotorasib)) with Amgen.
"We are pleased with the progress of our scientific collaborations and the high level of interest of leading investigators to advance the preclinical synergy data towards clinical evaluation of VS-6766 in combinations across multiple tumor types, including melanoma, colorectal and breast cancers," said Louis Denis, CMO of Verastem Oncology. "These clinical research efforts complement our company-sponsored development program and help to expediently advance our efforts to address an even broader scope of significant unmet medical needs."

About VS-6766

VS-6766 (formerly known as CH5126766 and RO5126766) is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. VS-6766 is currently in late-stage development.

In contrast to other MEK inhibitors, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK inhibitor VS-6766, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.1

Verastem Oncology is conducting Phase 2 registration-directed trials of VS-6766 alone and with defactinib in patients with recurrent LGSOC and in patients with recurrent KRAS G12V-mutant NSCLC as part of its RAMP (Raf And Mek Program) clinical trials, RAMP 201 and RAMP 202, respectively. Verastem Oncology has also established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and adagrasib in combination with VS-6766 in KRAS G12C-mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively.