On May 13, 2021 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 first quarter ended March 31, 2021 and provided an update on recent business highlights (Press release, Bolt Biotherapeutics, MAY 13, 2021, View Source [SID1234579920]).

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"Our successful IPO in the first quarter of 2021 places us in a position of strength to deliver on value-creating milestones in 2021 and 2022. We continue to advance our Phase 1/2 trial for our lead candidate, BDC-1001, for the treatment of patients with HER2-expressing solid tumors. We look forward to completing the monotherapy dose escalation and initiating the monotherapy Phase 2 dose expansion cohorts as well as the evaluation of combining BDC-1001 with an anti-PD-1 antibody later in 2021," said Randall C. Schatzman, Ph.D., Chief Executive Officer of Bolt. "Beyond BDC-1001, we continue to advance our pipeline and are on track to initiate clinical trials for CEA-targeted ISAC BDC-2034 in 2022 and we expect to designate our third clinical candidate later this year."

Recent Business Highlights and Anticipated Milestones

Cash, cash equivalents, and marketable securities were $302.9 million as of March 31, 2021, which is expected to fund operations into 2023 – Bolt is well positioned to continue to drive growth across the company and advance the pipeline through key milestones, with cash to fund operations into 2023.

Completed upsized Initial Public Offering in February 2021 – In February 2021, Bolt completed its Initial Public Offering (IPO) of 13,225,000 shares of common stock, inclusive of the full exercise by the underwriters of their option to purchase 1,725,000 shares, at a public offering price of $20.00 per share. Gross proceeds from the IPO were approximately $264.5 million and net proceeds from the offering, after deducting underwriting discounts, commissions and offering expenses, were approximately $242.0 million.

Presented on the HER2-targeting Boltbody ISAC BDC-1001 in the "New Drugs on the Horizon" symposium and in a trial-in-progress poster in April at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting

At AACR (Free AACR Whitepaper)’s New Drugs on the Horizon symposium, Bolt’s Chief Scientific Officer David Dornan, Ph.D. presented key data-driven decisions made during the development of Bolt’s lead program, BDC-1001, a novel HER2-targeting ISAC. Dr. Dornan’s presentation included a discussion of immunosuppression mediated by various cells in the tumor microenvironment (TME), as well as the tumor-supportive nature of antigen presenting cells (APCs) in the TME in preclinical models. Reawakening these immunosuppressed APCs can result in a productive and durable anti-tumor immune response, as evidenced by BDC-1001 achieving complete tumor regression in preclinical tumor models.
A Trial in Progress poster was also presented at AACR (Free AACR Whitepaper) by Manish R. Sharma, M.D. of START Midwest, a principal investigator in Bolt’s ongoing BDC-1001 Phase 1/2 trial. The poster detailed the design of the four-part study evaluating BDC-1001 administered intravenously with or without an immune checkpoint inhibitor targeting PD-1 in up to 390 patients with HER2-expressing or HER2-amplified advanced or metastatic solid tumors. The dose escalation parts will evaluate sequential doses of BDC-1001 as a monotherapy or in combination with a PD-1 checkpoint inhibitor in a 3+3 design, with the ability to backfill up to a total of 15 patients in each dose cohort. The dose expansion parts will evaluate the recommended Phase 2 dose as monotherapy or in combination with a PD-1 checkpoint inhibitor in four cohorts of patients. Bolt expects to provide a further update on the trial sometime in the second half of 2021.
Upcoming Events

At the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Manish R. Sharma, M.D. of START Midwest, a principal investigator in Bolt’s ongoing BDC-1001 Phase 1/2 trial will present a poster entitled "Preliminary results from a Phase 1/2 study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors." This poster will provide more details on the initial 20 patients treated with BDC-1001, as of the initial data cutoff date of January 29, 2021.
First Quarter 2021 Financial Results

Cash Position – Cash, cash equivalents, and marketable securities were $302.9 million as of March 31, 2021, compared to $22.8 million as of December 31, 2020. Bolt expects its cash balance to fund operations into 2023.

Research and Development (R&D) Expenses – R&D expenses were $14.1 million for the quarter ended March 31, 2021, compared to $6.8 million for the same quarter in 2020. The increase in R&D spending in the comparative periods was due primarily to increased manufacturing of BDC-1001 and BDC-2034 (CEA-targeting Boltbody ISAC program), increased personnel-related expenses due to additional hiring and increased facility-related expenses and outside services.

General and Administrative (G&A) Expenses – G&A expenses were $4.3 million for the quarter ended March 31, 2021, compared to $2.1 million for the same quarter in 2020. The increase in G&A spending in the comparative periods was due primarily to increased personnel-related expenses due to additional hiring and increased accounting and legal fees associated with the Company’s Initial Public Offering which was completed in February 2021.

Loss from Operations – Loss from operations was $24.5 million for the quarter ended March 31, 2021 compared to $8.6 million for the same quarter in 2020.

On May 13, 2021 Monopar Therapeutics Inc. (Monopar or the Company) (Nasdaq: MNPR), a clinical-stage biopharmaceutical company primarily focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported first quarter 2021 financial results and recent business updates (Press release, Monopar Therapeutics, MAY 13, 2021, View Source [SID1234579936]).

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Recent Business Updates

Validive

Monopar’s Phase 2b/3 VOICE clinical trial of Validive (clonidine HCl mucobuccal tablet) for the prevention of severe oral mucositis (SOM) in patients undergoing chemoradiotherapy (CRT) for oropharyngeal cancer (OPC) dosed its first patient in February 2021 and is actively recruiting patients and initiating additional clinical trial sites. There is no FDA-approved prevention or treatment for CRT-induced SOM.
The U.S. Patent and Trademark Office (USPTO) allowed a new patent with claims for Validive covering "Clonidine and/or clonidine derivatives for use in the prevention and/or treatment of adverse side effects of chemotherapy." This patent expands coverage on the potential uses of Validive in cancer patients beyond earlier allowed claims limited specifically to the prevention and/or treatment of oral mucositis in patients receiving CRT.
Camsirubicin and Novel Analogs

Based on the Company’s current inability to gain regulatory approval to initiate the camsirubicin Phase 2 clinical trial in Spain, Monopar is evaluating alternatives to move the dose escalation run-in clinical trial forward outside of Spain. Monopar believes that it will be able to initiate the run-in clinical trial in the second half of 2021 in the U.S. or another country.

The USPTO allowed a new patent with claims covering compositions of matter for a novel family of camsirubicin analogs (2-pyrrilino camsirubicins). This patent expires in 2038, not including any patent term extensions. The patent broadens Monopar’s camsirubicin portfolio and covers a pipeline of compounds designed to retain the potentially favorable non-cardiotoxic chemical backbone of camsirubicin along with the potent broad-spectrum antitumor activity of doxorubicin. Preclinical evidence suggests that this new family of 2-pyrrilino camsirubicin analogs could be active against doxorubicin-resistant tumor cells and thereby may enable use in cancer types beyond those treatable with doxorubicin.
MNPR-101 and Related Compounds

Progress continues in the Monopar/NorthStar Medical Radioisotopes collaboration focused on developing a novel treatment for severe COVID-19 by partnering with (1) IsoTherapeutics Group, LLC to develop, optimize and manufacture humanized urokinase plasminogen activator receptor radioimmunotherapeutics (uPRITs), (2) Aragen Bioscience, Inc. which performed studies to enable the selection of a lead candidate uPRIT along with back-up candidates to potentially advance into IND-enabling development, and (3) The University of Texas Health Science Center at Tyler and its Texas Lung Injury Institute (TLII) to perform in vitro and in vivo studies and to participate in the potential clinical development of uPRITs.
A peer-reviewed preclinical study that reported the potential utility of MNPR-101 conjugates as uPAR imaging agents to improve surgical outcomes in bladder cancer and for surveillance post-resection was published in The European Journal of Cancer. This publication builds on previous studies using conjugates of MNPR-101 and its mouse analog, ATN-658, for the optical imaging of oral and colon cancer.
A peer-reviewed study titled "Engineered Antibody Fragment against the Urokinase Plasminogen Activator for Fast Delineation of Triple-Negative Breast Cancer by Positron Emission Tomography" demonstrated the potential to identify breast cancers with urokinase plasminogen activator (uPA) overexpression, and monitor uPA expression during treatment using positron emission tomography (PET) imaging along with the Company’s uPA antibody fragment radiotracer.
Results for the First Quarter Ended March 31, 2021 Compared to the First Quarter Ended March 31, 2020

Cash and Net Loss

Cash and cash equivalents as of March 31, 2021 were $25.7 million. Monopar anticipates that its current cash and cash equivalents, which includes $10.9 million of net proceeds raised in the first quarter of 2021 under the Company’s Capital on DemandTM Sales Agreement with JonesTrading Institutional Services, at an average gross price per share of $10.20, will fund the Company’s major programs at least through June 2022, including: funding and completing the Phase 2b portion of the VOICE clinical trial and commencing of the Phase 3 portion; funding the camsirubicin run-in clinical trial; continuing advancement of the COVID-19 uPRIT program; and developing other MNPR-101 related compounds and technologies. The Company plans to raise additional funds and/or engage a partner within the next 12 months to complete the VOICE clinical program and continue the camsirubicin clinical development beyond the run-in clinical trial.

Net loss for the first quarter of 2021 was $1.9 million or $0.16 per share compared to net loss of $1.1 million or $0.10 per share for the first quarter of 2020.

Research and Development (R&D) Expenses

R&D expenses for the first quarter of 2021 were $1.2 million compared to $0.3 million for the first quarter of 2020. This increase of $0.9 million was primarily attributed to increases of (1) $0.3 million for the planning of the GEIS-sponsored camsirubicin Phase 2 clinical trial including drug product manufacturing, (2) $0.3 million for R&D personnel expenses, (3) $0.2 million for the VOICE clinical trial and manufacturing-related expenses, and (4) $0.1 million for other R&D operating expenses.

General and Administrative (G&A) Expenses

G&A expenses for the first quarter of 2021 were $0.7 million, a nominal decrease from $0.8 million of G&A expenses for the first quarter of 2020.

On May 13, 2021 Merus N.V. (Nasdaq: MRUS), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported new collaborations in Israel, Italy and Spain to expand molecular screening opportunities for patients with cancers that may have neuregulin 1 (NRG1) fusions and to raise awareness of the Merus eNRGy clinical trial of its bispecific antibody zenocutuzumab (Zeno) (Press release, Merus, MAY 13, 2021, View Source [SID1234579953]). In the collaborations, Merus plans to support molecular screenings for eligible patients with pancreatic adenocarcinoma in Israel and Italy, and with non-small cell lung cancer (NSCLC) in Spain, aimed to identify the presence of NRG1 fusions. Each collaborating organization in turn has agreed as follows:

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Progenetics, Ltd. plans to perform a nationwide campaign in Israel to raise awareness of the molecular screening offered by Merus for eligible pancreatic adenocarcinoma patients and availability of the eNRGy trial for eligible patients. Progenetics is a leading Israeli company in oncology testing, currently distributing diagnostic tests for nine American companies in the field of onco-diagnostics.

Italian Association for the Study of Pancreas (AISP) plans to inform their nationwide network of oncologists, pancreatic cancer patients and patient associations in Italy of the molecular screening offered by Merus for eligible pancreatic adenocarcinoma patients and availability of the eNRGy trial for eligible patients.

Dr. Michele Reni, a Principal Investigator on the eNRGy trial and physician at the San Raffaele Scientific Institute in Milan, has agreed to facilitate the collaboration with AISP and said, "Our collaboration with Merus, and the testing they are supporting, offers a unique opportunity to our patients and to physicians involved in the treatment of pancreatic cancer to help patients know their NRG1 fusion status and to potentially match patients with clinical trial opportunities that specifically target their unique tumor profiles."
Universidad de Navarra plans to provide Merus-funded molecular screening to eligible patients with NSCLC, through the Clínica Universidad de Navarra network in Spain, which may identify NRG1 fusions, and plans to inform patients with NRG1-fusion-positive cancer of their potential eligibility for the eNRGy trial. The Clínica Universidad de Navarra, based in Pamplona and Madrid, is a leading research hospital in Spain. A recognized institution for both its teaching and research work, and its trajectory in the diagnosis and treatment of highly complex pathologies, the Clínica Universidad de Navarra is characterized by the diagnostic speed achieved through multidisciplinary work and the acquisition of the latest technology to offer care in 46 different medical and surgical specialties.
"These latest collaborations expand Merus’ global efforts to raise awareness of the importance of molecular testing which can lead to potentially better treatment and clinical trial options for cancer patients," said Dr. Andrew Joe, Chief Medical Officer of Merus. "Merus’ support in the screening of these patients is also a strategic effort to potentially identify and recruit patients with cancer harboring NRG1 fusions for our eNRGy trial."

Merus has implemented a global approach designed to increase access to molecular screenings for cancer patients and to potentially enhance enrollment in the eNRGy trial by working with private industry, country-specific testing organizations, cooperative groups and disease-specific cancer organizations. Increasing access to molecular screenings may help oncologists and their patients, whose cancers may not be screened routinely for gene mutations, make informed decisions on what treatment and clinical trial options may be available.

With the addition of these collaborations announced today, Merus is now working with more than ten different industry and academic collaborators across Asia, North America and Europe aimed to enhance testing for NRG1 fusions and to raise awareness of the eNRGy trial.

About the eNRGy Clinical Trial
Merus is currently enrolling patients in the phase 1/2 eNRGy trial to assess the safety and anti-tumor activity of zenocutuzumab (Zeno) monotherapy in NRG1+ cancers. The eNRGy trial consists of three cohorts: NRG1+ pancreatic cancer; NRG1+ non-small cell lung cancer; and NRG1+ other solid tumors. Further details, including current trial sites, can be found at www.ClinicalTrials.gov and Merus’ trial website at www.nrg1.com or by calling 1-833-NRG-1234.

About NRG1 Fusions
The NRG1 gene encodes neuregulin (also known as heregulin), the ligand for HER3. Fusions between NRG1 and partner genes are rare, tumorigenic genomic events occurring in patients with certain cancers.

About Zeno
Zenocutuzumab (Zeno) is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions. Learn more about Zeno Dock & Block at View Source

On May 13, 2021 Elpiscience Biopharma, a clinical stage biopharma focusing on the discovery and development of next-generation cancer immunotherapies, reported the closing of Series C round of financing of 105 million USD (Press release, Elpiscience, MAY 13, 2021, View Source;id=1385 [SID1234580008]). This round of financing was led by the Greater Bay Area Homeland Development Fund, with participation from Cormorant Asset Management, Maison Capital, Superstring Capital, Pluto Connection Limited, Unifortune Fund etc. Existing investors, including Lilly Asia Ventures, CDH Investments, Dyee Capital and Oriza Holdings continued to invest in this round of financing.

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Proceeds raised from this round will be primarily used to expand the global reach of Elpiscience’s R&D strategy, i.e. as a start, to advance Elpiscience’s innovative molecules into clinical studies in the US. Part of the proceeds will also be used for exploring novel mechanisms of cancer immunotherapy and fueling more strategic partnerships.

"We are thrilled to have the continued support and endorsement from the top tier investors. It’s been a remarkable 3.5 years," said Dr. Darren Ji, Chairman and CEO of Elpiscience, "Elpiscience is determined to become a innovation leader in developing the next generation of cancer immunotherapies. We are committed to bringing at least one world-class molecule into the clinic each year to benefit cancer patients globally."

On May 13, 2021 Biogen Inc. (Nasdaq: BIIB) and Envisagenics reported a new collaboration to advance ribonucleic acid (RNA) splicing research within central nervous system (CNS) diseases (Press release, Biogen, MAY 13, 2021, View Source [SID1234580040]). As part of the collaboration, Biogen will leverage Envisagenics’ proprietary artificial intelligence (AI)-driven RNA splicing platform, SpliceCore, to define and understand the regulation of different RNA isoforms in CNS cell types.

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Genetic information encoded in the human chromosome is converted into RNA molecules which is then used as the template to make proteins. RNA splicing is the process that trims out extra information embedded in the intermediate RNA molecules, and this trimmed RNA is what is then used to produce functional proteins.

"Since Biogen’s earliest days, RNA splicing has been an integral part of our history and mission dating back to co-founder Phillip Sharp’s discovery of the process in 1977," said Alfred Sandrock, Jr., M.D., Ph.D., head of research and development at Biogen. "By combining Envisagenics’ SpliceCore platform with our deep expertise in this scientific approach, we believe that Biogen will be able to advance our understanding of RNA splicing and potentially identify new drug targets for CNS diseases."

"Envisagenics is thrilled to work with Biogen because we share a commitment to identifying potential treatments for CNS diseases through innovative AI technology like the SpliceCore platform. Envisagenics and Biogen recognize the power of RNA splicing to aid in the discovery of potential therapeutics," said Maria Luisa Pineda, Ph.D., chief executive officer of Envisagenics. Envisagenics’ Chief Technology Officer, Martin Akerman, Ph.D., added, "scientists have only recently been able to uncover disease-causing novel isoforms at scale, thanks to improvements in the speed and sensitivity of bioinformatics software like SpliceCore."

Traditionally, the process of detecting, cataloging and interpreting RNA splicing errors has been laborious, slow and costly. However, by tapping into Envisagenics’ machine learning algorithms and high-performance computing, Biogen may now be able to identify, test and validate splicing errors at scale. Through this collaboration, Biogen will gain access to SpliceCore’s database of approximately seven million potential RNA splicing errors, which is the largest database of splicing errors in the world. This will provide Biogen with a broader lens to evaluate splicing events that may be targeted for therapeutic gain. In addition, collaboration aligns to Biogen’s broader objective of identifying and validating genetic targets of disease to increase the probability of success in CNS drug discovery.