On March 30, 2022 Bolt Biotherapeutics, Inc. (NASDAQ: BOLT) a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported financial results for the fourth quarter and full year ended December 31, 2021, and provided an update on recent business highlights (Press release, Bolt Biotherapeutics, MAR 30, 2022, View Source [SID1234611219]).

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"In 2021, we demonstrated for the first time that our HER2-targeting Boltbody ISAC can increase myeloid cell infiltration and repolarize macrophages in the tumor microenvironment, and thereby, established proof of mechanism for our pioneering Boltbody ISAC platform. In our Phase 1/2 study, BDC-1001 was well tolerated at all dose levels tested with no dose-limiting toxicities. At the lower dose levels evaluated to date, we have seen stable disease in multiple different tumor types and a partial response that has now persisted for more than 60 weeks," said Randall C. Schatzman, Ph.D., Chief Executive Officer of Bolt Biotherapeutics. "We continue to explore dose levels expected to achieve our targeted higher drug exposures, and look forward to determining the recommended Phase 2 dose for BDC-1001 as monotherapy and in combination with Opdivo."

Recent Business Highlights

•Initiation of BDC-1001 combination arm with Bristol Myers Squibb’s PD-1 checkpoint inhibitor OPDIVO (nivolumab) in ongoing Phase 1/2 clinical trial for the treatment of patients with HER2-expressing solid tumors – In December 2021, Bolt Biotherapeutics dosed the first patient in a new combination arm of the ongoing multi-center, multi-dose Phase 1/2 clinical trial of BDC-1001.
•Reported interim Phase 1/2 monotherapy data for BDC-1001 in HER2-expressing solid tumors at ESMO (Free ESMO Whitepaper) I-O 2021 – In December 2021, Bolt Biotherapeutics presented a poster at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2021 detailing new safety, pharmacokinetic, and pharmacodynamic results from 57 subjects, 40 of whom were evaluable for efficacy, in the ongoing monotherapy dose-escalation portion of the Phase 1/2 trial. BDC-1001 demonstrated a favorable safety and tolerability profile. BDC-1001 also demonstrated early signs of clinical activity in the lower doses evaluable for efficacy with corresponding biomarker changes in the tumor microenvironment. The Company expects to determine the recommended Phase 2 dose for expansion trials in 2022.
•Advanced BDC-2034, a Boltbody ISAC targeting CEA, into IND-enabling studies with clinical development expected to begin in 2022 – Bolt Biotherapeutics is conducting IND-enabling studies with the goal of initiating clinical development in 2022. Data presented to date demonstrated tumor cell killing and innate immune activation in cellular and in vivo models of CEA-expressing cancers. Systemic administration in tumor-bearing animals was shown to result in dose-dependent anti-tumor activity.
•Presented preclinical data demonstrating progress of three novel anti-cancer therapeutic candidates at SITC (Free SITC Whitepaper) 2021 – In November 2021, Bolt Biotherapeutics presented three posters highlighting Bolt Biotherapeutics’ pipeline including BDC-2034, a PD-L1 Boltbody ISAC, and BDC-3042, an agonist antibody targeting Dectin-2, a novel target for tumor macrophage reprogramming in cancer immunotherapy.
•Expanded Bolt Biotherapeutics executive leadership team and board of directors with multiple appointments and promotions – The Company added Nicole Onetto, M.D., Brian O’Callaghan, and Frank Lee to the board of directors, bringing deep industry experience in clinical development and commercial strategy within oncology drug development. Jim Healy, M.D., Ph.D., assumed the role of Lead Independent Director. Additionally, Bolt Biotherapeutics promoted Bruce Hug, M.D., Ph.D., to Senior Vice President, Clinical Development & Translational Medicine, Nathan Ihle, Ph.D., to Senior Vice President, Pharmaceutical Operations, and Brian Safina, Ph.D., to Senior Vice President, Discovery Research.
•Cash, cash equivalents, and marketable securities were $271.6 million as of December 31, 2021, which is expected to fund operations and the advancement of the Company’s oncology product pipeline to achieve multiple key milestones into 2024.

Upcoming Events

•At the upcoming 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, the Company will present three posters highlighting preclinical research, demonstrating anti-tumor activity and supporting future clinical development for these novel, early-stage pipeline programs.
oWilliam G. Mallet, Ph.D., will present a poster entitled, "The CEA-targeted ISAC, BDC-2034, shows preclinical efficacy associated with innate immune activation, phagocytosis, and myeloid reprogramming" on Tuesday, April 12, 2022, from 9:00 a.m. – 12:30 p.m. CT.

oShelley E. Ackerman, Ph.D., will present a poster entitled, "Dectin-2 agonist antibodies reprogram tumor-associated macrophages to drive anti-tumor immunity" on Tuesday, April 12, 2022, from 9:00 a.m. – 12:30 p.m. CT.

oJustin Kenkel, Ph.D., will present a poster entitled, "PD-L1-targeted ISAC combines myeloid cell activation, immune-checkpoint inhibition and ADCP to improve anti-tumor efficacy over anti-PD-L1 antibodies in preclinical models" on Wednesday, April 13, 2022, from 9:00 a.m. – 12:30 p.m. CT.

•At the 21st Annual Needham & Co Virtual Healthcare Conference, management will be available for meetings with the investment community on Thursday, April 14, 2022, with a live virtual corporate presentation at 3:45 p.m. ET.

Fourth Quarter and Full Year 2021 Financial Results

Cash Position – Cash, cash equivalents, and marketable securities were $271.6 million as of December 31, 2021, compared to $22.8 million as of December 31, 2020. Bolt Biotherapeutics expects its cash balance to fund operations into 2024.

Collaboration Revenue – Revenue was $0.5 million for the quarter and $1.3 million for the full year ended December 31, 2021, compared to zero and $0.2 million for the same quarter and year in 2020. Revenue in 2021 was generated from services performed under the newly initiated R&D collaboration with Genmab A/S.

Research and Development Expenses – R&D expenses were $22.5 million for the quarter and $75.7 million for the full year ended December 31, 2021, compared to $14.9 million and $40.4 million for the same quarter and year in 2020, primarily due to increase in manufacturing and clinical trial expenses related to BDC-1001 and BDC-2034 and increase in personnel expenses relating to an increase in headcount.

General and Administrative Expenses – G&A expenses were $5.1 million for the quarter and $18.4 million for the full year ended December 31, 2021, compared to $2.1 million and $9.1 million for the same quarter and year in 2020, primarily due to increased expenses related to being a public company, including higher personnel expenses relating to increased headcount and an increase in professional services expenses.

Loss from Operations – Loss from operations was $27.1 million for the quarter and $92.8 million for the full year ended December 31, 2021, compared to $16.9 million and $49.2 million for the same quarter and year in 2020.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform

ISACs are a new category of immunotherapy combining the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs comprise three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, which can lead to the conversion of immunologically "cold" tumors to "hot" tumors with the goal of durable responses for patients with cancer.

On March 30, 2022 Keymed Biosciences Inc. (HKEX Code: 02162) reported 2021 annual results (Press release, Keymed Biosciences, MAR 30, 2022, View Source [SID1234611212]).

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BUSINESS HIGHLIGHTS

On July 8, 2021, Keymed was listed on the HKEX. During the Reporting Period, the Company continued proceeding the R&D of products and made the following progress with respect to pipeline and business operation:

Rapid development of in-house discovered products
Core product CM310 (IL-4Rα antibody):

The Company has initiated and completed the Phase IIb clinical trial for moderate-to-severe AD in adults, with the results disclosed in November 2021. And the Phase III clinical study has been rapidly initiated in the first quarter of 2022.
Phase II clinical trial for patients with CRSwNP was initiated in the first half of 2021 and the enrollment was completed in September 2021, and the results were disclosed in March 2022. The Company plans to initiate the Phase III study for CRSwNP in the second half of 2022.
Core product CM326 (TSLP antibody):

The Company has initiated and completed the Phase I trial in healthy persons in 2021, with the results disclosed in November 2021.
Phase Ib/IIa clinical trials of CM326 in adults with moderate to severe AD have been initiated in the first quarter of 2022.
Phase Ib/IIa clinical trials in patients with CRSwNP are about to be initiated.
Core product CMG901 (Claudin 18.2 ADC):

Phase I clinical trial of CMG901 in subjects with solid tumors was proceeded in 2021, which is currently in the dose-escalation phase. The Company expects to initiate the dose-expansion stage of trial in solid tumors in China in the second quarter of 2022.
In March 2021, Keymed received the FDA IND clearance of CMG901 for the Phase I clinical trial in gastric and GEJ cancers in the U.S.
CM313 (CD38 antibody):

The Phase I clinical trial for hematologic malignancies including RRMM and lymphoma was initiated and proceeded in 2021. The dose-escalation trial is expected to be completed in the first half of 2022.
In January 2022, Keymed submitted a clinical trial application to the NMPA for the indication of CM313 in the treatment of SLE.
Rapid expansion of workforce and production facilities
By the end of 2021, the Company had more than 320 employees, including over 120 employees engaging in clinical development and operations.
In addition to the headquarters in Chengdu, the Company has offices in Shanghai, Beijing, Wuhan, Guangzhou, etc.
In 2021, the Company initiated the construction of a new plant in Chengdu, and the first production line is expected to be put into operation in mid-2022 with capacity of 16,000 L. The designs of all facilities are in compliance with the requirements of cGMP of the NMPA and FDA.
Actively cooperation with external parties

In 2021, Keymed entered into cooperation with CSPC in respect to the interests in China (excluding Hong Kong, Macau and Taiwan) of CM310 and CM326 in respiratory disease indications such as moderate-to-severe asthma and COPD. In September 2021, the Company strategically allied with CSPC to jointly identify, research, develop and commercialize one or more nervous system disease-related products.

In 2021, Keymed entered into a strategic collaboration agreement with InnoCare to develop first-in-class large-molecule innovative drugs.

Financial Position

As of December 31, 2021, the Company’s R&D investment totaled RMB360 million; the collaboration income is RMB110 million, which was mainly derived from the cooperation with CSPC and InnoCare.
As of December 31, 2021, the Company’s cash in hand is approximately RMB3.5 billion.

On March 30, 2022 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer and infectious diseases, reported the initiation of a Phase 1 trial evaluating its novel chimeric antigen receptor T-cell (CAR-T) therapy in ovarian cancer (Press release, Anixa Biosciences, MAR 30, 2022, View Source [SID1234611211]). The CAR-T approach used for Anixa’s therapy is known as chimeric endocrine receptor T-cell (CER-T) since the target of the engineered T-cells is an endocrine receptor. The Phase 1 trial at Moffitt Cancer Center will evaluate the safety and efficacy of Anixa’s therapy in patients with ovarian cancer. Anixa holds an exclusive, worldwide license for the technology, which was developed at the Wistar Institute.

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While CAR-T therapy has shown efficacy in some hematological tumors, reproducing the same results with solid tumors, such as ovarian cancer, has proven challenging. One of the reasons for this difficulty is that effective CAR-T therapy needs a specific antigen to recognize that is only present on target cancer cells in order to avoid negatively affecting healthy cells. The CER-T therapy being evaluated in Anixa’s Phase 1 study differs from traditional CAR-T in that it targets the follicle stimulating hormone receptor (FSHR), which research indicates is exclusively expressed on ovarian cells in healthy adult females.

"We are thrilled to have partnered with world-class scientists at Moffitt Cancer Center to advance our CER-T platform and feel that this partnership provides a critical opportunity to make a significant impact on the treatment of solid tumors," said Dr. Amit Kumar, President, CEO and Chairman of Anixa Biosciences. "We strongly believe that our unique targeting approach differentiates our CER-T platform from traditional CAR-T approaches and that CER-T has potential to work in solid tumors where other therapies have failed."

Jose R. Conejo-Garcia, M.D., Ph.D., Chair of the Department of Immunology at Moffitt Cancer Center and co-inventor of the CER-T technology, added, "CAR-T therapies are rapidly becoming an important player in cancer therapy, and our lab has developed a technology that has the potential to target tumors by using an existing biological mechanism that is well understood. If our CER-T approach is successful, it could serve as a model for future targeted CAR-T therapies in other cancer types. The goal in cancer therapy has always been to kill cancer cells with limited damage to healthy tissue, and we look forward to seeing how this CER-T therapy may be able to accomplish that in solid tumors, which have historically proven challenging to eradicate with cell therapy."

Robert Wenham, M.D., MS, FACOG, FACS, the trial’s lead investigator and Chair of the Department of Gynecologic Oncology at Moffitt Cancer Center, added, "There are limited treatment options for recurrent, chemo-resistant ovarian cancer, and this platform holds immense promise to change that. I am hopeful that this program represents a unique opportunity for us to potentially make a truly game-changing impact for patients with ovarian cancer and other solid tumors."

About Anixa’s CER-T Approach (Follicle Stimulating Hormone Receptor-Mediated CAR-T technology)
Anixa’s chimeric antigen receptor T-cell (CAR-T) technology approach is an autologous cell therapy comprised of engineered T-cells that target the follicle stimulating hormone receptor (FSHR). FSHR is found at immunologically relevant levels exclusively on the granulosa cells of the ovaries. Since the target is a hormone (chimeric endocrine) receptor, and the target-binding domain is derived from its natural ligand, this technology is known as CER-T (chimeric endocrine receptor T-cell) therapy, a new type of CAR-T.

On March 30, 2022 Sutro Biopharma, Inc. ("Sutro" or the "Company") (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer therapeutics, reported that the company presented on advances with its novel immunostimulatory antibody-drug conjugate (iADC) modality at the 12th Annual World ADC conference taking place virtually and in London, from March 29 through April 1, 2022 (Press release, Sutro Biopharma, MAR 30, 2022, View Source [SID1234611210]).

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Sutro’s novel iADC modality was generated with Sutro’s proprietary and integrated cell-free protein synthesis platform and site-specific conjugation platform. The molecule allows for a single therapy to target tumors with conjugated toll-like receptor (TLR) agonist in addition to a conjugated cytotoxic warhead. The iADC modality provides for dual mechanisms to attacking the tumor, through cytotoxic killing as well as potentially building a protective immune response. Using dual conjugations to deliver both components as systemic therapy potentially broadens the types of tumors that can be treated.

"This novel iADC modality is a further confirmation of the fruitful journey at Sutro, building upon a decade of research working with precisely conjugated ADCs," commented Trevor Hallam, Ph.D., President of Research and Chief Scientific Officer of Sutro. "Sutro’s novel iADC technology has therapeutic potential in difficult-to-treat cancers by both directly targeting cancer cells and activating the patient’s own immune system through the dual mechanism of action. With this technology, we can potentially develop an off-the-shelf therapy that aims to program a patients natural immune response to treat cancer and protect against future disease."

Dr. Hallam presented virtually at a session during the pre-conference seminar titled, "A New Molecular Class to target Tumor Immunity by both disrupting the tumor and enabling the immune system" on Tuesday, March 29, 2022.

Arturo Molina, M.D., M.S., FACP, Chief Medical Officer of Sutro, presented a session titled "Targeting FolRα in Gynecologic Cancers & other Solid Tumours with the Novel Antibody-Drug Conjugate, STRO-002," on Wednesday, March 30. The talk examined nonclinical and clinical data of STRO-002 in ovarian, endometrial, and other cancers, including the previously disclosed interim dose-expansion data of STRO-002-GM1.

The presentations will be accessible through the News & Events page of the company’s website at www.sutrobio.com.

On March 30, 2022 Everest Medicines (HKEX 1952.HK), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products to address critical unmet needs in Asia Pacific markets, reported that it has submitted a New Drug Application (NDA) to the Department of Health, the Hong Kong Special Administrative Region, China for sacituzumab govitecan (SG) for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) in adult patients who have received two or more prior systemic therapies, at least one of them for metastatic disease (Press release, Everest Medicines, MAR 30, 2022, View Source [SID1234611209]).

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"This submission reinforces the ongoing momentum in the development of SG throughout Asia, bringing this medicine one step closer to patients in yet another important region in Asia, and adding to the growing number of regulatory applications under active review," said Yang Shi, Chief Medical Officer for Oncology at Everest Medicines. "As women diagnosed with mTNBC have historically had minimal treatment options available to them and breast cancer has become the most common cause of death in women in Hong Kong over the past few decades, this application is especially timely. We look forward to moving closer to our goal of making SG an accessible treatment option for women throughout Greater China."

Everest is also closely coordinating with regulatory bodies in mainland China, South Korea and Taiwan to review its applications for SG for adult patients with unresectable locally advanced or mTNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease. In February 2022, Everest announced the approval of Trodelvy (trade name for SG) in Singapore for second-line mTNBC.

In November 2021, Everest announced topline results for its Phase 2b EVER-132-001 study of SG, which met its primary endpoint with a 38.8% overall response rate (ORR). This study evaluated 80 people in China, and the results were consistent with those from the global Phase 3 ASCENT study, thus showing similar efficacy in the Chinese population.

About Triple-Negative Breast Cancer (TNBC)

TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. The median age of breast cancer diagnoses tends to be younger in Asian than western countries, and the percentage of the TNBC molecular subtype has been increasing in the past 10 years. TNBC cells do not have estrogen and progesterone receptors and have limited human epidermal growth factor receptor 2 (HER2). Due to the nature of TNBC, effective treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of metastatic breast cancer.

About Sacituzumab Govitecan (SG)

Sacituzumab govitecan (SG) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. SG is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

SG is approved in more than 35 countries, with additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic TNBC, under the trade name Trodelvy. SG is also approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

SG is also being developed for potential investigational use in other TNBC and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.

Under a licensing agreement with Gilead Sciences, Inc., Everest Medicines has exclusive rights to develop, register, and commercialize SG for all cancer indications in Greater China, South Korea, and certain Southeast Asian countries. In October 2020, SG was included in the updated 2020 China Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer, compiled by the Breast Cancer Expert Committee of the National Cancer Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Cancer Drug Clinical Research Professional Committee of the Chinese Anti-Cancer Association.