On March 15, 2022 Biognosys, a leader in next-generation proteomics solutions for drug discovery and development, and Kymera Therapeutics, a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD), reported that they are broadly collaborating across preclinical studies and clinical trials (Press release, Biognosys, MAR 15, 2022, View Source [SID1234610133]).

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Proteome editing with TPD is a new frontier of medicine, aimed at expanding the druggable proteome. Biognosys’ TrueSignature platform uniquely offers high-precision proteomic panels that provide actionable insights based on highly specific and sensitive, absolute quantification of pharmacodynamic and efficacy biomarkers. These custom panels allow Kymera to monitor and quantify protein degradation. The ease of transferability of the assays — from early discovery, across preclinical evaluation, to clinical development — enables integration into all stages of Kymera’s drug development process. The panels are developed and performed at Biognosys’ state-of-the-art facility, the largest high-end, GLP certified and GCP compliant mass spectrometry laboratory worldwide for large-scale proteomics contract research.

"Kymera’s novel approach to targeted protein degradation is a great example of the power of proteomics-enabled drug development," said Kristina Beeler, Ph.D., Chief Business Officer of Biognosys. "We are glad to see the impact our TrueSignature platform is having, not only on the advancement of Kymera’s clinical trial programs, but also on patients’ lives."

The current partnership between Kymera and Biognosys builds upon the longstanding scientific relationship between the two companies across early R&D, preclinical, and clinical settings across oncology and inflammation.

"Biognosys has been a valued partner as we continue to expand our clinical pipeline across a diverse set of diseases and indications," said Nello Mainolfi, Ph.D., Co-Founder, President and CEO, Kymera Therapeutics. "The company’s high-precision custom proteomics panels enable us to monitor and quantify protein degradation across all aspects of drug development, including preclinical and clinical programs."

About TrueSignature

The Biognosys TrueSignature platform provides high-precision customizable proteomics panels for pharmacodynamic readouts and clinical biomarker monitoring.

Parallel Reaction Monitoring mass-spectrometry powers the platform, allowing complete customization and independence from affinity-based recognition and reagent availability. The TrueSignature panels offer an unprecedented level of multiplexing, enabling the simultaneous absolute quantification of up to 100 proteins.

TrueSignature panels can be developed within weeks and are available both as a standalone solution or an integrated solution, in which insights from TrueDiscovery studies guide the choice of proteins in the custom panel. The measurements are performed with unprecedented speed and throughput at Biognosys’ state-of-the-art facility, the world’s largest high-end GLP-certified and GCP-compliant mass spectrometry laboratory. For more information, visit truesignature.bio

On March 15, 2022 BostonGene Corporation and Thomas Jefferson University reported the online publication of the manuscript, "Tadalafil enhances immune response to neoadjuvant nivolumab in resectable head and neck squamous cell carcinoma" in the American Association for Cancer Research (AACR) (Free AACR Whitepaper) journal Clinical Cancer Research (Press release, BostonGene, MAR 15, 2022, View Source [SID1234610132]). The study revealed pretreatment head and neck squamous cell carcinoma specimens contain distinct HPV status-dependent signatures predictive of immunotherapy response, while post-treatment specimens treated with combination nivolumab and tadalafil exhibit tumor immune microenvironments enriched with B and natural killer cell-associated gene signatures.

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The study evaluated the molecular, cellular and immunologic profiles of head and neck cancer patients treated with nivolumab alone versus combined nivolumab and tadalafil. The first arm received nivolumab, a PD-1 inhibitor, intravenously on days 1 and 15 prior to surgery on day 28. The second arm received the same treatment with the addition of daily oral tadalafil, a PDE5 inhibitor, during the 28 days before surgery. Groups were stratified by HPV status. Imaging, blood, and tumor tissue obtained at pre- and post-treatment time points were used for correlative analysis. For the analysis BostonGene applied its integrated whole exome and whole transcriptome workflow to simultaneously assess the tumor and tumor microenvironment profiles. The results show the tumor proliferation rate is a negative predictor of response, while T cells are predictive of a positive response in HPV-negative head and neck cancer patients. The addition of tadalafil to traditional PD-1 inhibitor therapy increases B and natural killer cell signatures present in post treatment biopsies of therapy responders. Overall, the results of the study demonstrates adding tadalafil to nivolumab in head and neck cancers advocates for further trials of PDE-5 inhibition in this context.

Adam J. Luginbuhl, M.D., Associate Professor of Otolaryngology at Thomas Jefferson University, and researcher at the Sidney Kimmel Cancer Center – Jefferson Health, says, "The study provides a comprehensive analysis of patient response to immune checkpoint inhibitors in both HPV-positive and HPV-negative head and neck cancers and can serve as a foundation for further studies on PDE-5 inhibition."

"Collaborating with Thomas Jefferson University underscores our commitment to improving the landscape of therapies for precision cancer medicine," says Nathan Fowler, MD, Chief Medical Officer at BostonGene. "We hope to see additional clinical trials demonstrating that signatures predictive of immunotherapy response benefit head and neck cancer patients in neoadjuvant settings."

On March 15, 2022 The Jerome Canady Research Institute for Advanced Biological and Technological Sciences (JCRI-ABTS), reported that their recent article, "BCL2A1 REGULATES CANADY HELIOS COLD PLASMA-INDUCED CELL DEATH IN TRIPLE-NEGATIVE BREAST CANCER (TNBC)", has been published in Scientific Reports, a Nature Portfolio journal (Press release, JCRI-ABTS, MAR 15, 2022, View Source [SID1234610131]). This novel discovery marks a significant advancement in cold plasma technology for cancer treatment.

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JCRI-ABTS’s scientists demonstrated that a combination of Canady Helios Cold Plasma (CHCP) and anti-BCL2A1 treatment may be beneficial and a novel therapeutic option for triple-negative breast cancer and other solid tumor cancers.

BCL2A1 expression plays an important role in cell survival after CHCP treatment in breast cancer cells and is potentially regulated by TNF-alpha. Silencing BCL2A1 by siRNA treatment or by downregulating its expression by CPI203 treatment in combination with CHCP significantly increases the potency of the CHCP treatment.

Breast cancer is the leading cause of cancer death among women. Triple-negative breast cancer (TNBC) has a very poor prognosis and frequent relapses occur early compared with other cancer subtypes. CHCP is proving to be a promising therapy for a variety of prognostically poor breast cancer types and BCL2A1 could be a potential companion diagnostic biomarker.

According to Jerome Canady, MD, Chief Science Officer, "We investigated the expression profile of 48 apoptotic and 35 oxidative gene markers after CHCP Treatment during this study, and we are pleased to report Canady Helios Cold Plasma induced cell death in the TNBC cell lines".

Dr. Taisen Zhuang, CTO of USMI revealed, "These outstanding results, discovered by our scientists, provide the solid theoretical foundation and will boost the commercialization process of Cold Plasma Oncotherapeutics. Patients with TNBC will benefit from our cold plasma technology in the near future".

JCRI-ABTS and sister company USMI have recently successfully completed a Phase 1 Clinical Trial using Canady Helios Cold Plasma (CHCP) for the treatment of recurrent and stage 4 solid tumors (FDA IDE #G190195).

On March 15, 2022 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported financial results for the quarter and full-year ended December 31, 2021, and provided an update on recent accomplishments and upcoming events (Press release, Syros Pharmaceuticals, MAR 15, 2022, View Source [SID1234610130]).

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"2021 was a pivotal year for Syros, marked by the initiations of three clinical trials and one expansion cohort across our targeted hematology and CDK inhibitor portfolios, promising data from our SY-5609 program, as well as the appointments of two key leadership team members," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "We believe we are well-positioned to build on this momentum in 2022. We expect three data readouts this year, including pharmacokinetic and safety data from our dose confirmation trial of SY-2101 in APL as well as clinical activity data from the safety lead-in portions of the SELECT-AML-1 Phase 2 trial and the expansion cohort of SY-5609 in pancreatic cancer. These results have the potential to deliver important insights into each of our investigational medicines as we continue to advance towards becoming a fully integrated biopharmaceutical company with the aim to make a profound difference for patients."

UPCOMING MILESTONES

Targeted Hematology

Tamibarotene: Oral RARα agonist

Report clinical activity data from safety lead-in portion of ongoing SELECT-AML-1 Phase 2 trial in newly diagnosed unfit RARA-positive patients with acute myeloid leukemia (AML) in the second half of 2022.
Report data from ongoing SELECT-MDS-1 Phase 3 trial in newly diagnosed RARA-positive patients with higher-risk myelodysplastic syndrome (HR-MDS) in the fourth quarter of 2023 or first quarter of 2024, with a potential new drug application (NDA) filing expected in 2024.
SY-2101: Oral arsenic trioxide (ATO)

Report pharmacokinetic (PK) and safety data from ongoing dose confirmation trial in newly diagnosed acute promyelocytic leukemia (APL) patients in mid-2022.
Initiate Phase 3 trial in first quarter of 2023 with data expected in 2025.
CDK Inhibition

SY-5609: Oral Selective CDK7 Inhibitor

Report clinical activity data from safety lead-in portion of ongoing expansion cohort evaluating SY-5609 in combination with chemotherapy in relapsed/refractory metastatic pancreatic cancer patients in the second half of 2022.
Roche plans for the arm of its ongoing Phase 1/1b INTRINSIC trial investigating SY-5609 in combination with atezolizumab in BRAF-mutant colorectal cancer (CRC) to be open for enrollment in the first half of this year. Under the terms of our agreement with Roche, Roche is the sponsor of the trial and Syros is supplying SY-5609.
Initiate Phase 1 trial evaluating SY-5609 in relapsed/refractory hematologic malignancies in the second half of 2022, with initial data expected mid-2023.
Gene Control Discovery Engine

Plan to present new preclinical data on the CDK12 inhibitor program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place from April 8-13.
Nominate next development candidate, a CDK12 inhibitor, in the second half of 2022.
RECENT PIPELINE HIGHLIGHTS

In February, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to tamibarotene for the treatment of HR-MDS. The FDA’s Office of Orphan Drug Products grants orphan status to support development of medicines for the treatment of rare diseases that affect fewer than 200,000 people in the United States. Orphan drug designation may provide certain benefits, including a seven-year period of market exclusivity if the drug is approved, tax credits for qualified clinical trials and an exemption from FDA application fees.
CORPORATE

In March, Syros entered into a Master Collaboration Agreement with QIAGEN to develop and commercialize an assay as a companion diagnostic for Syros’ proprietary RARA biomarker for use with tamibarotene in newly diagnosed HR-MDS patients. QIAGEN will also be responsible for obtaining and maintaining regulatory approvals for the commercial diagnostic test.
FOURTH QUARTER AND FULL YEAR 2021 FINANCIAL RESULTS

Revenues were $7.8 million for the fourth quarter of 2021, consisting of $6.5 million in revenue recognized under Syros’ collaboration with Global Blood Therapeutics, Inc. (GBT) and $1.3 million recognized under its collaboration with Incyte Corporation (Incyte). Revenues were $23.5 million for the year ended December 31, 2021, consisting of $19.4 million and $4.1 million from Syros’ collaborations with GBT and Incyte, respectively. Syros recognized $5.7 million in revenue in the fourth quarter of 2020, consisting of $3.6 million in revenue recognized under its collaboration with GBT and $2.1 million recognized under its collaboration with Incyte, and $15.1 million for the year ended December 31, 2020, consisting of $11.7 million and $3.4 million from its collaborations with GBT and Incyte, respectively.
Research and development expenses were $26.8 million for the fourth quarter of 2021 and $99.9 million for the year ended December 31, 2021, as compared to $29.0 million for the fourth quarter of 2020 and $76.1 million for the year ended December 31, 2020. The decrease for the fourth quarter of 2021 compared to the same period in 2020 was primarily due to the purchase of SY-2101 in the fourth quarter of 2020. The increase for the year ended December 31, 2021 was primarily due to the increase in costs associated with the continued advancement of our clinical and preclinical programs and employee-related expenses.
General and administrative (G&A) expenses were $6.4 million for the fourth quarter of 2021 and $23.0 million for the year ended December 31, 2021, as compared to $5.9 million for the fourth quarter of 2020 and $21.3 million for the year ended December 31, 2020.
For the fourth quarter of 2021, Syros reported a net loss of $23.8 million, or $0.38 per share, compared to a net loss of $30.1 million, or $0.62 per share, for the same period in 2020. For the full year ended December 31, 2021, Syros reported a net loss of $86.6 million, or $1.38 per share, compared to a net loss of $84.0 million, or $1.82 per share, for the same period in 2020.
Cash and Financial Guidance

Cash, cash equivalents and marketable securities as of December 31, 2021 were $143.4 million, as compared with $174.0 million on December 31, 2020. This change reflects cash used to fund Syros’ operations during the full year ended December 31, 2021, partially offset by gross proceeds of $75.6 million that Syros received from its January 2021 public offering.

Based on its current plans, Syros believes that its existing cash, cash equivalents and marketable securities will be sufficient to fund its planned operating expenses and capital expenditure requirements into the first quarter of 2023.

Conference Call and Webcast

Syros will host a conference call today at 8:30 a.m. ET to discuss these fourth quarter and full year 2021 financial results and provide a corporate update.

To access the live conference call, please dial (866) 595-4538 (domestic) or (636) 812-6496 (international) and refer to conference ID 9682507. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation.

On March 15, 2022 Epizyme (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering transformative therapies for cancer patients against novel epigenetic targets, reported a clinical update as well as the appointment of Jerald Korn as Chief Operating Officer, reporting to President and Chief Executive Officer, Grant Bogle (Press release, Epizyme, MAR 15, 2022, View Source [SID1234610129]).

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"We are excited to welcome Jerald to Epizyme at a pivotal time for the organization," said Mr. Bogle. "Jerald’s breadth of experience leading a wide range of functions and working in biotech companies at our stage of development will be a welcomed addition to our senior executive team as we look to drive growth for TAZVERIK (tazemetostat) as a monotherapy, as well as advance the tazemetostat clinical development program across both hematologic and solid tumor malignancies."

"I am thrilled to be joining Epizyme at such an important time for the company," said Mr. Korn. "I have a passion for working in the oncology space and am excited by the opportunity to help execute on the continued launch of TAZVERIK and to fulfill Epizyme’s vision of developing transformative epigenetic medicines. I look forward to working alongside this incredible team as we focus on the strategic priorities where we believe we can make a meaningful impact for people living with cancer."

With more than 15 years in the biotech industry, Mr. Korn most recently served as the Chief Operating Officer and General Counsel at Kaleido Biosciences, where he oversaw legal, human resources, program management, quality, regulatory and other operations, as well as supporting the company with corporate strategy, including two financings, a pipeline prioritization and transition to a new laboratory and manufacturing facility. Prior to Kaleido, Mr. Korn held several leadership positions at TESARO, as well as senior positions at Cubist Pharmaceuticals, Millennium Pharmaceuticals (part of Takeda) and AMAG Pharmaceuticals. Mr. Korn began his career as an associate at the law firm Ropes & Gray and holds a bachelor’s degree with honors in economics from Harvard University and a J.D. with honors from Boston University School of Law.

SYMPHONY-1 Clinical Update

Epizyme also reported today that the first patient has been dosed in the Phase 3 portion of the SYMPHONY-1 (EZH-302) study, a confirmatory study assessing tazemetostat in combination with rituximab + lenalidomide (R2) compared with R2 plus placebo in patients with relapsed or refractory follicular lymphoma (R/R FL) previously treated with at least one systemic therapy, including those who are rituximab-refractory and/or have experienced progression of disease within two years.

"Dosing the first patient in the Phase 3 portion of the SYMPHONY-1 study is an important milestone for Epizyme and our clinical development of tazemetostat in R/R FL," said Dr. Shefali Agarwal, Executive Vice President and Chief Medical and Development Officer at Epizyme. "As we enroll patients in the Phase 3 randomized portion of the study, we plan to continue to report longer term follow-up data from the Phase 1b safety run-in portion of the study as well as data from other combination studies of tazemetostat in both hematological and solid tumor malignancies that we are conducting."

Epizyme previously announced the completion of the 30-day waiting period for its protocol amendment submitted to the U.S. Food and Drug Administration in December 2021 with 800 mg twice-daily as the recommended Phase 3 dose. The Company is now engaged in global start-up activities, including sites in greater China with its collaboration partner HUTCHMED. The latest results of the Phase 1b safety run-in portion of the study were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021 and can be accessed here.

About TAZVERIK (tazemetostat)

TAZVERIK is a methyltransferase inhibitor indicated for the treatment of:

Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications is contingent upon verification and description of clinical benefit in confirmatory studies.

The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.