On March 2, 2023 Prostate Cancer Foundation reported that Immunotherapies have successfully treated many types of cancer with the exception of advanced prostate cancer that has become resistant to treatment, known as metastatic castration-resistant prostate cancer (mCRPC) (Press release, Prostate Cancer Foundation, MAR 2, 2023, View Source [SID1234628102]). New findings from a Prostate Cancer Foundation (PCF)-funded investigator reveal the mechanism by which prostate cancer cells reprogram the immune system to promote rather than suppress cancer, as well as a promising new combination therapy that could prevent them from developing this ability.

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The research led by 2016 Izzy Englander – PCF Challenge Award recipient Akash Patnaik, MD, PhD, MMSc, and his team at the University of Chicago was recently published in the peer-reviewed journal Clinical Cancer Research.

"These findings represent an exciting new opportunity to prevent prostate cancer cells from evading the immune system and a promising combination therapy for metastatic castration-resistant prostate cancer," said Howard R. Soule, PhD, Executive Vice President and Chief Science Officer of the Prostate Cancer Foundation. "PCF commends Dr. Patnaik and the research team on their achievement and proudly supports their work to bring us closer to our mission to eliminate death and suffering from prostate cancer."

Researchers found that by recruiting abnormal tumor-associated macrophages (TAM) that express PD-1 into the tumor microenvironment, the immune system promotes the growth of prostate cancer.

Androgen deprivation therapy (ADT) and chemotherapy are first-line treatment options for metastatic prostate cancer. However, patients often relapse and the disease advances. Nearly 35,000 men in the U.S. are projected to die of prostate cancer in 2023.

Approximately 50% to 75% of mCRPC patients have a mutation in the tumor suppressor gene PTEN which drives the PI3K tumor growth and survival pathway; in patients with PTEN-mutated tumors, the normal anti-tumor immune response is often suppressed. Alterations of the PTEN/PI3K pathway are known drivers of advanced prostate cancer. Clinical trials of single drugs to target this pathway and combinations of PI3K inhibitors and ADT have shown limited benefit in patients with mCRPC.

Patnaik and his team performed a series of experiments using PTEN-mutated mouse models. They found that following treatment with a combination of ADT and copanlisib, a PI3K inhibitor, PD-1-expressing immunosuppressive TAM blocked the anti-cancer immunity mediated by macrophages; the cancer cells forced the macrophages into tumor-promoting mode by binding to the protein PD-1 on their surface. The researchers hypothesized that adding a third drug to block PD-1 would unleash the ability of the macrophages to kill the cancer. The triple combination of PD-1 checkpoint immunotherapy plus ADT hormone therapy plus a PI3K inhibitor yielded a response rate 60% greater among treated mice than among untreated control mice. These data suggest that the three-drug approach is needed to overcome treatment resistance in PTEN-mutated prostate cancer.

As part of the PCF Challenge Award, a phase 1b clinical trial will be conducted to test the safety and efficacy of copanlisib in combination with an anti-PD-1 drug in patients with PTEN-deficient mCRPC. If successful, the research could result in a new precision immunotherapy regimen for these patients.

On March 2, 2023 Arcus Biosciences (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported that its management team will participate in a fireside chat at the upcoming Barclays Global Healthcare Conference in Miami Beach, Florida (Press release, Arcus Biosciences, MAR 2, 2023, View Source [SID1234628101]). The fireside chat will take place on Tuesday, March 14th, 2023 at 8:30 a.m. ET.

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A live webcast of the fireside chat will be available by visiting the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay of the webcast will be available following the live event.

On March 2, 2023 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported that its Board of Directors has appointed Christopher Hall as Chief Executive Officer (CEO) and a member of the Board, effective immediately, in addition to his role as President (Press release, Personalis, MAR 2, 2023, View Source [SID1234628100]). Hall will lead the Company’s efforts to drive a new paradigm for the active management of cancer with the aim of guiding care from biopsy throughout the life of the patient. Hall joined Personalis in October 2022 and became President at the end of December 2022.

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The Board also promoted Aaron Tachibana to the extended leadership position of Chief Operating Officer (COO), effectively immediately, in addition to his role as Chief Financial Officer (CFO). Tachibana served as Interim CEO since the end of December 2022, and has served as CFO since joining Personalis in 2019, when he led the Company through its initial public offering. In addition, Dr. Richard Chen has been promoted to the position of Executive Vice President, R&D, effective immediately, in addition to his role as Chief Medical Officer (CMO). Dr. Chen, who joined Personalis in 2011 as Chief Scientific Officer, was previously Senior Vice President, R&D and CMO.

"This is a momentous time for Personalis, and we are confident that with this leadership team, we can deliver on our potential to create a new paradigm for the way cancer is actively managed," said Karin Eastham, Board Chair of Personalis. "The Board thanks Aaron for his role as Interim CEO for the past two months. He, Chris, and Rich led a strategic overhaul to focus on three core areas: winning in the minimal residual disease (MRD) space, enabling customers to develop personalized cancer vaccines, and supporting biopharmaceutical customers with their clinical trials. They have also taken prudent steps to reduce our cash burn, focus on improving margins, and work toward future profitability."

Added Eastham, "We are thrilled to welcome Chris, Aaron, and Rich into their new roles, building upon a strong foundation as Personalis evolves into a diagnostic product company and as a critical partner in cancer recurrence detection and therapy monitoring."

"Since its founding, Personalis has emerged as a genomics technology leader, a sequencing powerhouse, and as a trusted partner to many of the world’s leading pharmaceutical companies," said Hall, Personalis’ President and CEO. "I’m excited about the future of this company and honored to be appointed as CEO to lead us into our next chapter. We believe we have one of the most discerning technologies to both characterize and monitor cancer, setting us up to become the leader in MRD detection and, ultimately, to help usher in a new standard of care in oncology."

Hall has several decades of experience in the diagnostic space, previously serving as CEO of Naring Health, a multi-omics company; President and COO of Veracyte; and as SVP and Chief Business Officer of Celera’s cardiovascular testing business. Hall earned an M.B.A. from Harvard University and a B.A. from DePauw University.

Tachibana has served in CFO and operational leadership roles in multiple public companies, focusing on improving gross margins and profitability. Tachibana holds a B.S. in Business Administration and Finance from San Jose State University.

Dr. Chen has decades of industry and academic experience in clinical medicine and oncology, innovative diagnostic and scientific product development, data science and genomics. He has co-founded several companies in the life sciences, including Ingenuity Systems, a pioneer in genomics and systems biology analytics for biopharma. Dr. Chen received a B.S. in Computer Science, an M.S. in Biomedical Informatics, and an M.D. from Stanford University.

About Personalis

On March 2, 2023 Click Therapeutics, Inc. ("Click"), a leader in Digital Therapeutics as prescription medical treatments, reported that company management will participate in two investor conferences this month (Press release, Click Therapeutics, MAR 2, 2023, View Source [SID1234628099]).

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Cowen 43rd Annual Health Care Conference: March 6-8, 2023 in Boston, MA
Barclays Global Healthcare Conference: March 14-16, 2023 in Miami, FL
Company management will participate in one-on-one meetings at both conferences. To request a meeting with the company, please reach out to the respective conference organizers.

On March 2, 2023 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, reported financial results for the quarter and full-year ended December 31, 2022 and provided a corporate update (Press release, Syros Pharmaceuticals, MAR 2, 2023, View Source [SID1234628098]).

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"In 2022, we advanced our efforts to develop new standards of care for the frontline treatment of hematologic malignancies, announcing promising data from our ongoing studies in AML and APL and progressing our pivotal trial in HR-MDS," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "We believe we are well-positioned to build on this progress in the year ahead. We are also encouraged by the continued momentum in our global enrollment for SELECT-MDS-1. As evidenced by the FDA’s recent decision to grant Fast Track Designation to tamibarotene for HR-MDS, there is a clear need for new therapies that can address the needs of people living with this progressive and devastating disease and we are working with urgency, together with physicians around the world, to recruit and enroll the SELECT-MDS-1 trial. In addition, we have initiated the randomized portion of the SELECT-AML-1 Phase 2 trial and are actively screening patients. We expect to report initial data from SELECT-AML-1 in the fourth quarter of this year and to provide an update on the development path and timing for further evaluation of SY-2101 in a registration-enabling study in APL in the second half of this year."

Dr. Simonian continued, "Following our strategic financing in 2022, we are operating from a position of financial strength, with sufficient capital to fund our efforts into the second quarter of 2025. Importantly, we expect that this capital will bring us beyond Phase 3 data from the SELECT-MDS-1 trial and initial data from the randomized portion of the SELECT-AML-1 trial, while also allowing us to begin investing in the commercial infrastructure that will be necessary to deliver our products to patients."

UPCOMING MILESTONES

Tamibarotene: Higher-Risk Myelodysplastic Syndrome (HR-MDS)

Complete patient enrollment in the SELECT-MDS-1 Phase 3 trial in newly diagnosed HR-MDS patients with RARA gene overexpression in the fourth quarter of 2023.
Report pivotal complete response (CR) data from the SELECT-MDS-1 Phase 3 trial in the third quarter of 2024.
Tamibarotene: Acute Myelodysplastic Syndrome (AML)

Announce initial data from the randomized portion of the SELECT-AML-1 Phase 2 trial in newly diagnosed unfit AML patients with RARA overexpression in the fourth quarter of 2023.
Report additional data from the SELECT-AML-1 Phase 2 trial in 2024.
SY-2101: Acute Promyelocytic Leukemia (APL)

Provide an update on the dose confirmation study of SY-2101, as well as the development path and timing for further evaluation of SY-2101 in a registration-enabling study in APL, in the second half of 2023.
RECENT PIPELINE HIGHLIGHTS

Initiated the randomized portion of the SELECT-AML-1 study and ­­patient screening. The study is designed to evaluate the safety and efficacy of tamibarotene in combination with venetoclax and azacitidine compared to venetoclax and azacitidine in approximately 80 patients with RARA overexpression, randomized 1:1. The primary endpoint is composite complete response (cCR) rate.
In February 2023, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to tamibarotene for the treatment of HR-MDS. Fast Track is a process designed by the FDA to facilitate the development and expedite the review of drugs that have the potential to treat serious conditions and address recognized areas of unmet medical need.
In December 2022, Syros announced the publication in Blood Advances of results from the completed biomarker-directed Phase 2 trial of tamibarotene in combination with azacitidine in newly diagnosed unfit AML patients. In patients with RARA gene overexpression, the combination of tamibarotene and azacitidine demonstrated a cCR rate of 61%, with a rapid onset and clinically meaningful durability. In patients with low blast count AML, the CR rate was 67%. In addition, correlative analyses of RARA expression levels identified an association of RARA overexpression with a monocytic gene expression signature that may be associated with resistance to venetoclax. Together, these data support Syros’ ongoing evaluation of tamibarotene for the treatment of AML and MDS patients with RARA overexpression.
At the 64th American Society for Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2022, Syros presented data from six response-evaluable patients in the safety lead-in portion of the ongoing SELECT-AML-1 Phase 2 trial. Treatment with the triplet combination of tamibarotene, venetoclax and azacitidine in patients with RARA overexpression demonstrated an 83% cCR rate and rapid onset of action, with no evidence of increased toxicity relative to historical data of the venetoclax and azacitidine doublet combination.
In December 2022, Syros also extended the research term under the collaboration agreement with Global Blood Therapeutics (GBT), now a part of Pfizer, for an additional year.
Fourth Quarter and Full Year 2022 Financial Results

Revenues were negative $0.8 million for the fourth quarter of 2022, as compared to $7.8 million in the fourth quarter in 2021. This decrease reflects a cumulative catch-up adjustment of revenue recognized under Syros’ collaboration with GBT as a result of extending the term of the research collaboration by one year. Revenues were $14.9 million for the year ended December 31, 2022, consisting of $13.6 million and $1.3 million from Syros’ collaborations with GBT and Incyte, respectively and $23.5 million for the year ended December 31, 2021.
Research and development expenses were $27.9 million for the fourth quarter of 2022 and $111.9 million for the year ended December 31, 2022, as compared to $26.8 million for the fourth quarter of 2021 and $99.9 million for the year ended December 31, 2021. The increase for the fourth quarter of 2022 compared to the same period in 2021 and the increase for the year ended December 31, 2022 compared to the year ended December 31, 2021 were primarily due to the increase in costs associated with the continued advancement of our clinical programs and employee-related expenses.
General and administrative (G&A) expenses were $7.3 million for the fourth quarter of 2022 and $29.3 million for the year ended December 31, 2022, as compared to $6.4 million for the fourth quarter of 2021 and $23.0 million for the year ended December 31, 2021.
Transaction-related expenses of $9.5 million for the year ended December 31, 2022 primarily consist of incurred costs allocated to the warrants issued in connection with the PIPE financing that were accounted for as liabilities, and severance paid to former Tyme employees following our acquisition of Tyme in September 2022.
For the fourth quarter of 2022, Syros reported a net loss of $4.8 million, or $0.17 per share, compared to a net loss of $23.8 million, or $3.78 per share, for the same period in 2021. For the full year ended December 31, 2022, Syros reported a net loss of $94.7 million, or $7.49 per share, compared to a net loss of $86.6 million, or $13.84 per share, for the same period in 2021.
Cash and Financial Guidance

Cash, cash equivalents and marketable securities as of December 31, 2022 were $202.3 million, as compared with $143.4 million on December 31, 2021.

Based on its current plans, Syros believes that its existing cash, cash equivalents and marketable securities will be sufficient to fund its anticipated operating expenses and capital expenditure requirements into the second quarter of 2025, beyond Phase 3 data from the SELECT-MDS-1 trial and initial data from the randomized portion of the SELECT-AML-1 trial.

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 2022 financial results and provide a corporate update.

To access the live conference call, please dial (888) 575-5167 (domestic) or (416) 764-8687 (international) and refer to conference ID 74534085. 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.