On March 17, 2022 Century Therapeutics, Inc., (NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology, reported financial results and business highlights for the fourth quarter and year ended December 31, 2021 (Press release, Century Therapeutics, MAR 17, 2022, View Source [SID1234610253]).

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"Throughout 2021, we continued to make steady progress in developing our comprehensive, next-generation iPSC-based cell therapy platform, executed on our powerful discovery engine, and we believe we are positioned to transition to a clinical stage company in 2022. With this foundation in place, we are on track to advance multiple product candidates to the clinic over the next three years," said Lalo Flores, Chief Executive Officer, Century Therapeutics. "Additionally, we look forward to continuing our partnership in the years ahead with Bristol Myers Squibb, a global leader in oncology and hematology, to further expand our pipeline of iPSC-derived cell therapy products for treating hematological and solid tumor malignancies. We are committed to maximizing the potential utility of our platform technology and look forward to what we expect to be a very productive year ahead."

Business Highlights

Entered into a collaboration and license agreement with Bristol Myers Squibb in January 2022 to develop and commercialize up to four iPSC-derived, engineered natural killer cell (iNK) and / or T cell (iT) programs for hematologic malignancies and solid tumors. Under the terms of the agreement, Century received a $100 million upfront payment and Bristol Myers Squibb made a $50 million equity investment in Century Therapeutics’ common stock. The agreement provides for future program initiation fees and development, regulatory, and commercial milestone payments totaling more than $3 billion plus royalties on product sales.
Announced that, subject to U.S. Food and Drug Administration (FDA) acceptance of its Investigational New Drug (IND) application, the Company plans to initiate a Phase 1 trial, ELiPSE-1, to assess CNTY-101 in patients with relapsed/refractory aggressive lymphoma or indolent lymphoma after at least two prior lines of therapy, including patients who have received prior CAR T cell therapy. In vivo data presented at the Annual Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December demonstrated strong antitumor activity against human lymphoma cell lines with CNTY-101.
Announced plans to focus its initial T cell development program on γδ cells. Data presented at the ASH (Free ASH Whitepaper) Annual Meeting in December suggest that γδ CAR-iT cells provide an opportunity to deliver allogeneic T cell therapies without risk for graft-versus-host disease. CNTY-102 will be a CAR- γδ iT candidate targeting CD19, and a second antigen for relapsed/refractory B cell lymphoma and other B cell malignancies.

Added to the NASDAQ Biotechnology Index (NASDAQ: NBI) in December 2021.
Upcoming Milestones

Current Good Manufacturing Practice (cGMP) manufacturing facility expected to be operational in 2022.
CNTY-101 IND filing remains on track for mid-2022. Subject to U.S. FDA acceptance of its IND application, the Company plans to initiate the Phase 1 ELiPSE-1 trial of CNTY-101 in relapsed/refractory lymphoma in 2022.
Expect to submit an IND for CNTY-103 in 2023. CNTY-103 is Century’s first solid tumor candidate for glioblastoma.
Fourth Quarter and Year-end 2021 Financial Results

Cash Position: Cash, cash equivalents, and marketable securities were $358.8 million as of December 31, 2021, as compared to $76.8 million as of December 31, 2020. Net cash used in operations was $89.0 million for the twelve months ended December 31, 2021, compared to $41.3 million for the twelve months ended December 31, 2020.
Research and Development (R&D) expenses: R&D expenses were $75.6 million for the year ended December 31, 2021, compared to $39.7 million for the year ended December 31, 2020. The increase in R&D expenses was primarily due to an increase in personnel expenses related to increased headcount to expand the Company’s R&D capabilities, costs for preclinical studies, costs for laboratory supplies, and facility costs.
General and Administrative (G&A) expenses: G&A expenses were $19.2 million for the year ended December 31, 2021, compared to $9.5 million for the year ended December 31, 2020. The increase was primarily due to an increase in personnel related expense due to an increase in employee headcount and an increase in the Company’s professional fees as a result of expanded operations to support its infrastructure as well as additional costs to operate as a public company.
Net loss: Net loss was $95.8 million for the year ended December 31, 2021, compared to $53.6 million for the year ended December 31, 2020.
Financial Guidance

The Company expects full year GAAP Operating Expenses to be between $155 million and $165 million including non-cash stock-based compensation expense of $10 million to $15 million.
The Company expects its cash, cash equivalents, and marketable securities, including proceeds from the Bristol Myers Squibb collaboration agreement, will support operations into 2025.

On March 17, 2022 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported financial results for the twelve months ended December 31, 2021, and provided a business update (Press release, Onconova, MAR 17, 2022, View Source [SID1234610269]).

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Highlights for the fourth quarter of 2021 and recent weeks include:

The Phase 1 solid tumor trials of narazaciclib in the United States and China are ongoing with no dose-limiting toxicities observed to date. The trial in the United States is currently enrolling into its fourth dose cohort, which is evaluating a 160 mg daily dose administered orally on each day of a 28-day treatment cycle. The trial in China is enrolling into its fifth dose cohort, which is evaluating a 200 mg dose administered orally once a day on days 1-21 of a 28-day treatment cycle. A protocol amendment is being prepared to enable further dose escalation in the trial in China.
Rigosertib’s investigator-sponsored program has seen progress across multiple trials. This is highlighted by continued enrollment in the dose expansion portion of the Phase 1/2a study of oral rigosertib plus nivolumab in patients with KRAS+ non-small cell lung cancer (NSCLC). Additionally, recent single-patient data from a heavily pre-treated participant in the Phase 2 trial of rigosertib monotherapy in advanced squamous cell carcinoma associated with recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) showed a durable complete response without signs of metastatic disease.
The Company strengthened its team with the appointment of Adar Makovski Silverstein, Ph.D., as Director, Corporate Development.
Management Commentary

"The advancements made across our pipeline over the past months have us on track for an exciting 2022," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "We continue to be pleased with the safety findings from narazaciclib’s ongoing Phase 1 program and remain on track to identify a recommended Phase 2 dose in the second half of the year. Narazaciclib shows low nanomolar activity against kinases associated with tumor growth, metastasis, and potentially drug resistance, which differentiates it from currently approved CDK 4/6 inhibitors. We thus believe it may have broad therapeutic potential in monotherapy and combination settings, both in patients showing resistance to approved CDK 4/6 inhibitors and in indications where these agents are not currently approved. Narazaciclib’s clinical development plan is designed to test this hypothesis, and we look forward to its continued progress."

Dr. Fruchtman continued, "Beyond our lead program in narazaciclib, we also reported compelling preliminary clinical data from an investigator-sponsored study of rigosertib in RDEB-associated SCC. These data showed a sustained complete response in a patient that was unresponsive to several prior treatments. Though from a single patient, we believe these data represent a potentially powerful observation in this ultra-rare indication given its invariably fatal nature and the lack of effective therapies. Rigosertib’s additional investigator-sponsored trials have also shown strong progress, as we are on track to report updated data from the Phase 1/2a study evaluating rigosertib-nivolumab combination therapy in KRAS+ NSCLC this year, and to open a Phase 2 metastatic melanoma trial of oral rigosertib plus pembrolizumab in the first half. Looking ahead, we will continue to leverage the collaborations that form the basis of these trials to pursue rigosertib’s clinical development across multiple indications while remaining primarily focused on our lead narazaciclib program."

Full Year Financial Results

Cash and cash equivalents as of December 31, 2021, were $55.1 million, compared with $19.0 million as of December 31, 2020. The Company believes that its cash and cash equivalents will be sufficient to fund ongoing clinical trials and business operations for at least two years.

Research and development expenses were $7.3 million for 2021, compared with $16.9 million for 2020. The decrease was primarily related to the Company’s focus on its Phase 1 program with narazaciclib, following the completion of the Phase 3 INSPIRE study in 2020.

General and administrative expenses were $9.4 million for 2021, compared with $8.3 million for 2020. The increase was primarily related to costs related to special and annual general meeting expenses in the 2021 period.

Net loss for 2021 was $16.2 million, or $0.96 per share on 16.8 million weighted average shares outstanding, compared with a net loss of $25.2 million, or $2.17 per share for 2020 on 11.6 million weighted average shares outstanding.

Conference Call and Webcast

Onconova will host an investment community conference call today beginning at 4:30 p.m. Eastern Time, during which management will discuss financial results for 2021, provide a business update, and answer questions. Interested parties can participate by dialing (855) 428-5741 (domestic callers) or (210) 229-8823 (international callers) and using conference ID 8097917.

A live webcast of the conference call will be available in the Investors & Media section of the Company’s website at www.onconova.com. A replay of the webcast will be available on the Onconova website for 90 days following the call.

On March 17, 2022 Biological Dynamics, Inc. reported the publication of its study, Early-Stage Multi-Cancer Detection Using an Extracellular Vesicle Protein-Based Blood Test, published in Nature Communications Medicine (Press release, Biological Dynamics, MAR 17, 2022, View Source [SID1234610287]). The test correctly identified 71 percent of stage 1 cancers in a combined cohort of pancreatic, ovarian, and bladder cancers with pancreatic stage 1 cancer detection at 96%.

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"The results are remarkable and highlight exosomal protein markers as a viable candidate for early-stage cancer detection," said Scott Lippman, M.D., co-senior author of this report and Director of UC San Diego Moores Cancer Center. "Specifically, pancreatic cancer is notoriously difficult to detect at an early stage, when surgery, the only curative therapy, is possible. Biological Dynamics’ assay is demonstrating the potential for early-stage cancer detection to be included in the standard of care."

The case-controlled pilot study explored a cohort of 139 pathologically staged patients with stage 1 and stage 2 pancreatic, ovarian, and bladder cancers. While other liquid biopsy approaches have shown high sensitivity in the later stages of cancer progression, they have been relatively unsuccessful in detecting cancers in earlier stages. Results from the study demonstrate that the company’s unique proprietary Verita platform can rapidly isolate extracellular vesicles (EVs) from 250 microliters of plasma and provide a multi-marker, protein-based analysis that clearly discriminates early-stage cancer cases from healthy controls. The method enables a unique, rapid, multiomic assessment from a single small blood draw.

"Our study shows effective use of EVs isolated by the Verita platform for early cancer detection," said Dr. Paul R. Billings, Biological Dynamic’s CEO and Director. "In addition to delivering the current exo-protein analysis, the platform can provide data on other exo-proteins, exosomal nucleic acids, and circulating DNA biomarkers. With our own development and in partnership, we intend to rapidly improve cancer detection and management."

Publication of this study follows Breakthrough Device Designation granted by the U.S. Food and Drug Administration (FDA) in October 2021. It reviewed Biological Dynamic’s liquid biopsy assay, Exo-PDAC, which delivers early-stage detection of pancreatic ductal adenocarcinoma (PDAC), an aggressive and lethal form of cancer growing in incidence worldwide.

On March 17, 2022 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the filing of a Phase 1 clinical trial for HLX301, a Recombinant Humanized Anti-PDL1 and Anti-TIGIT Bispecific Antibody (BsAb), in Patients with advanced tumours has been approved by the National Medical Products Administration (NMPA) (Press release, Shanghai Henlius Biotech, MAR 17, 2022, View Source [SID1234610986]). At present, no bispecific antibody targeting PD-1/PD-L1 and TIGIT has been approved for marketing globally. In February 2022, the first patient was dosed in Australia in Phase 1 clinical trial of HLX301, ahead of the same class of BsAb targeting PD-L1×TIGIT, making HLX301 potentially the first-in-class anti-PD-L1×TIGIT BsAb.

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TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domains) is an inhibitory receptor, mainly expressed on natural killer (NK) cells and activated CD8+ T cells, CD4+ T cells, and T regulatory cells. As an inhibitory receptor, TIGIT can inhibit innate and adaptive responses in various mechanisms of action and act as a "brake" like PD-1/PD-L1 does to stop T cells from attacking tumours. Pre-clinical studies reported that HLX301 can simultaneously block both PD-1/PDL1 and TIGIT/PVR pathways, restore TCR signaling, inhibit tumour growth, and has good tolerance and safety, paving the way for further clinical development to against a variety of advanced tumours, including non-small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, etc.

Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with many emerging targets, including PD-1/L1, LAG-3, TIGIT, BRAF, etc., and has been pushing its early R&D research capabilities further while also upgrading the technology platform. The company is currently taking effort to explore different forms of antibody conjugates based on our own core antibody technologies and by using of novel conjugating technologies. Looking forward, Henlius is actively accelerating its evolution to an innovative Biopharma and improving efficiency through innovations. It will preserve its momentum for innovation by further strengthening the in-licensing and collaboration on external innovative assets and bringing more high-quality and affordable therapies to patients worldwide.

On March 17, 2022 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL inhibitors for severe unmet medical needs, reported the publication of a peer-reviewed article entitled "AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1+ CD8+ T cells" in the journal Cell Reports Medicine (Press release, BerGenBio, MAR 17, 2022, View Source [SID1234610215]).

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The article reports on research that identifies AXL as a critical targetable driver of immune suppression in STK11/LKB1 mutated non-small cell lung cancer (NSCLC). Mutations in STK11/LKB1 in NSCLC occur in approximately 20% of patients and are associated with poor outcomes and limited response to immune checkpoint blockade, commonly utilized treatments for lung cancer.

This article and its accompanying material are accessible here:

View Source(22)00060-X

The research was led by Professor Rolf A. Brekken, in the Hamon Center for Therapeutic Oncology Research at theUT Southwestern Medical Center. The group introduced a STK11/LKB1 mutation into a preclinical murine model of lung adenocarcinoma, resulting in immune checkpoint blockade refractory tumors. The group posits that the lack of response occurred because the STK11/LKB1 mutated tumors lacked a specific population of immune cells (TCF1-expressing CD8+ immune T cells). This immune cell population was also reduced in human NSCLC tumors carrying STK11/LKB1 mutations.

Systemic inhibition of AXL by the BerGenBio molecule bemcentinib led to increased type I interferon secretion from AXL-expressing dendritic cells, resulting in expansion of the TCF1+ T cell population and restored therapeutic response to immune checkpoint blockade treatment. These results were observed in both an immunocompetent mouse model and in mice bearing human STK11/LKB1 mutant NSCLC tumors along with a humanized immune system. The paper also summarizes clinical data in NSCLC patients with identified STK11/LKB1 mutations receiving bemcentinib and immune checkpoint blockage (pembrolizumab), who demonstrated objective clinical response to combination therapy.

In November 2021 BerGenBio announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for bemcentinib in combination with an anti-PD-(L)1 agent as a treatment for patients with STK11/LKB1 altered advanced/metastatic NSCLC patients without actionable mutations.

Martin Olin, Chief Executive Officer of BerGenBio, commented: "We are pleased to receive this strong preclinical validation of the potential role of bemcentinib to treat STK11/LKB1 mutated NSCLC patients. Data suggests that this significant patient population is underserved by current immune checkpoint blockade therapies, and we hope that the combination with bemcentinib can restore the immune response in these patients. The identification of a new druggable biomarker segment such as the STK11/LKB1 mutations may offer significant hope for improved patient outcomes in combination with the current standard of care therapies. We look forward to initiating a clinical trial this year to advance bemcentinib into development for this patient population."