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.