On March 26, 2020 Bolt Biotherapeutics, Inc., a private biotechnology company developing its Immune-Stimulating Antibody Conjugate (ISAC) platform technology to harness the power of the immune system to treat cancer, reported that patient dosing has begun in the company’s Phase 1, open-label, dose-escalation and dose expansion study of BDC-1001 monotherapy for patients with HER2-expressed solid tumors (Press release, Bolt Biotherapeutics, MAR 26, 2020, View Source [SID1234555887]). BDC-1001 is an ISAC comprised of trastuzumab conjugated to Bolt’s proprietary TLR7/8 agonist payload.

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"The initiation of this study represents a significant milestone for the company as it is our first Boltbody therapeutic program to enter the clinic," stated Randall Schatzman, Ph.D., chief executive officer of Bolt. "Bolt’s leadership in the ISAC field will continue to drive the development of myeloid-based cancer therapeutics. There is a significant unmet need for patients with solid tumors that express HER2 that cannot be addressed by current immuno-oncology therapeutics."

Dr. Schatzman continued, "Based on an assessment of our ongoing program by the safety committee, we are now proceeding with the second cohort of our study. Bolt is eager to explore the potential of BDC-1001 for treating HER2-expressing cancers, which includes patients with breast and gastric cancers that are refractory to Herceptin and Kadcyla, as well as cancers for which no HER2-targeting therapies have yet been approved. We look forward to working with the medical community to bring the promise of this exciting new approach to patients and anticipate initial data will drive our future development plans."

The program has generated compelling preclinical data demonstrating complete, durable regression of established tumors resistant to trastuzumab and immunological memory providing protection against tumor cells that no longer express the HER2 antigen in syngeneic mouse cancer models.

About the BDC-1001 Phase 1 Study in HER2-Expressed Solid Tumors
The Phase 1, multi-center, open-label study will evaluate the safety, pharmacokinetics, pharmacodynamics and proof of mechanism of BDC-1001 in HER2-expressing solid tumors. The first portion of the study includes a monotherapy dose-escalation phase in which cohorts of patients will receive ascending intravenous doses of BDC-1001 to determine the maximum tolerated dose and/or the recommended dose for the expansion cohorts and Phase 2 based on safety and tolerability. The second portion of the study is a dose expansion phase in which patients will receive BDC-1001 monotherapy to evaluate antitumor activity of the recommended Phase 2 dose and to further evaluate the safety and tolerability of BDC-1001. Please refer to clinicaltrials.gov NCT04278144 for additional clinical trial information.

About Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) Platform Technology
The Boltbody platform consists of Immune Stimulating Antibody Conjugates (ISACs) that harness the ability of innate immune agonists to convert cold tumors into immunologically hot tumors thereby illuminating tumors to the immune system and allowing them to be invaded by tumor killing cells. Boltbody ISACs have demonstrated the ability to eliminate tumors following systemic administration as monotherapy in preclinical models and have also led to the development of immunological memory, which is predicted to translate into more durable clinical responses for patients.

On March 26, 2020 Moffitt Cancer Ctr reported that the survival rates for patients with non-small cell lung cancer (NSCLC) have improved greatly over the past decade thanks to several new targeted treatment options for patients (Press release, Moffitt Cancer Ctr, MAR 26, 2020, View Source [SID1234555969]). However, lung cancer still remains the number one cause of cancer-related morality, leading to approximately 154,000 deaths each year in the United States. Many patients do not respond to these new targeted therapies or they may develop drug resistance. Researchers at Moffitt Cancer Center are trying to identify alternative strategies to treat this disease. In a new article published online in Scientific Reports, they highlight how targeting the histone deacetylase HDAC11 may be a novel therapeutic strategy for NSCLC.

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Histone deacetylases (HDACs) are proteins that regulate the expression and activity of genes by altering DNA compaction and modifying proteins. HDACs are often deregulated in different types of cancer and several drugs that inhibit HDACs have been approved to treat these diseases. HDAC11 is one of the newest HDACs to be identified, but its role in cancer is not yet known.

Moffitt researchers conducted a series of preclinical studies to investigate the role of HDAC11 in NSCLC. They discovered that high levels of HDAC11 are found in samples from patients with NSCLC and that these high levels are associated with poor survival. The research team wanted to further delineate the potential role of HDAC11 in NSCLC development. They focused their studies on cancer stem cells (CSCs), which are slowly dividing cells that can undergo self-renewal. CSCs are known to contribute to tumor development and progression and are also highly resistant to chemotherapy and targeted drug treatments.

"It has been suggested that drugs that can eliminate CSCs would be effective as anti-cancer agents and could potentially overcome drug resistance," said Srikumar Chellappan, Ph.D., chair of the Department of Tumor Biology at Moffitt.

Chellappan and his team discovered that HDAC11 is found at high levels in CSCs and is associated with expression of the protein Sox2 – a gene that is highly important for the self-renewal of CSCs. When the researchers targeted HDAC11 in NSCLC with specific inhibitors, they observed that the ability of CSCs to undergo self-renewal and expression of Sox2 were greatly reduced. Given the importance of CSCs to lung cancer growth and development, these observations suggest that targeting HDAC11 may be a potential strategy to block the self-renewal process of CSCs and inhibit NSCLC progression.

In additional studies, the research team found that these specific HDAC11 inhibitors impacted several processes associated with cancer development, including the formation of vascular networks, anchorage independent growth and cell motility. The HDAC11 inhibitors also reduced the growth of lung cancer cells that were resistant to other targeted therapies and inhibited the growth of lung cancer cells grown in the presence of other cells that contribute to drug resistance.

"This study presents a mechanistic basis for the role of HDAC11 in lung adenocarcinoma and suggests that once the parameters for in vivo studies and efficacy are met, they would be of immense potential in combating NSCLC," said Chellappan.

The study was supported by a Moffitt Innovation Grant and FORMA Therapeutics.

On March 26, 2020 Bristol-Myers Squibb Company (NYSE: BMY) reported that it will announce results for the first quarter of 2020 on Thursday, May 7, 2020 (Press release, Bristol-Myers Squibb, MAR 26, 2020, View Source [SID1234555848]). During a conference call at 8:30 a.m. ET on May 7, 2020, company executives will review financial information and address inquiries from analysts.

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Investors and the general public are invited to listen to a live webcast of the call at bms.com/investors or by dialing in the U.S. toll free 888-256-1007 or international 1-786-789-4797, confirmation code: 3261903. Materials related to the call will be available at the same website prior to the conference call. A replay of the call will be available beginning at 12 p.m. ET on May 7 through 12 p.m. ET on May 21, 2020. The replay will also be available through bms.com/investors or by dialing in the U.S. toll free 888-203-1112 or international 1-719-457-0820, confirmation code: 3261903.

On March 26, 2020 IntelGenx Technologies Corp. (TSX V:IGX)(OTCQX:IGXT) (the "Company" or "IntelGenx") reported financial results for the fourth quarter and twelve-month periods ended December 31, 2019 (Press release, IntelGenx, MAR 26, 2020, View Source [SID1234555872]). All dollar amounts are expressed in U.S. currency, unless otherwise indicated, and results are reported in accordance with United States generally accepted accounting principles except where noted otherwise.

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2019 Fourth Quarter Financial Highlights:

Revenue was $68,000, compared to $651,000 in the 2018 fourth quarter
Adjusted EBITDA was ($2.1 million), compared to ($2.0 million) in Q4-2018
2019 Full-Year Financial Highlights:

Revenue was $742,000, compared to $1.8 million in 2018
Net comprehensive loss was $10.3 million, compared to net comprehensive loss of $10.6 million in 2018
Adjusted EBITDA was ($8.5 million), compared to ($7.9 million) in 2018
Recent Highlights:

Closed an offering of 16,317,000 units (the "Units") at a price of C$0.50 per Unit for gross proceeds of C$8.2 million.
Received a No Objection Letter from Health Canada in response to IntelGenx’s amended Clinical Trial Application for the ongoing Montelukast VersaFilm Phase 2a ("BUENA") clinical trial in patients with mild to moderate Alzheimer’s Disease.
Announced that a cannabis-infused VersaFilm product has been finalized with its co-development partner, Tilray, Inc. (NASDAQ:TLRY) ("Tilray") and all manufacturing scale-up work has been successfully completed.
Signed a binding term sheet with Orivas for the commercialization of RIZAPORT pursuant to which Orivas will obtain exclusive rights to market and sell RIZAPORT in Lithuania, Latvia, Estonia and Poland, with the right of first refusal for a predefined term to include the Republic of Belarus and/or the Republic of Ukraine, as well as any of the Scandinavian countries (Finland, Denmark, Sweden and Norway).
"There are several very near-term milestones that represent potential value inflection points for our Company," said Dr. Horst G. Zerbe, CEO of IntelGenx. "We are anticipating receipt of the U.S. Food and Drug Administration’s decision on our 505(b)(2) New Drug Application for RIZAPORT VersaFilm for the treatment of acute migraines later today. On the heels of that, we also expect to receive Health Canada’s requisite micro-processing license in the coming weeks, which will enable us to begin commercial production of cannabis-infused oral films for our partner, Tilray, with product sales expected to begin as soon as practicable thereafter. In addition, we are planning to resume enrollment for our Phase 2a BUENA trial at our Canadian sites under a Health Canada-approved dose increase and are looking forward to providing initial trial data as they become available."

Financial Results:

Total revenues for the three-month period ended December 31, 2019 amounted to $68,000, a decrease of $583,000 compared to $651,000 for the three-month period ended December 31, 2018. The change is mainly attributable to a decrease in R&D revenues of $583,000. Operating costs and expenses were $2.4 million for the fourth quarter 2019, versus $2.9 million for the corresponding three-month period of 2018. For Q4-2019, the Company had an operating loss of $2.4 million, compared to operating loss of $2.2 million for the comparable period of 2018.

Total revenues for the twelve-month period ended December 31, 2019 amounted to $742,000, compared to $1.8 million for the twelve-month period ended December 31, 2018. Operating costs and expenses were $10.3 million for the full year 2019, versus $10.8 million for the corresponding 12-month period of 2018. For the twelve-month period of 2019, the Company had an operating loss of $9.6 million, compared to an operating loss of $9.0 million for the comparable period of 2018. Net comprehensive loss was $10.3 million, or $0.11 per basic and diluted share, for the twelve-month period of 2019, compared to net comprehensive loss of $10.6 million, or $0.14 per basic and diluted share, for the comparable period of 2018.

As at December 31, 2019, the Company’s cash and short-term investments totalled $1.9 million, which did not include gross proceeds of C$8.2 million raised by the Company in its February 2020 equity offering.

Annual Filings:

The Company’s annual report on Form 10-K and financial statements for the year ended December 31, 2019, as well as its 2020 Proxy Statement, will be filed with the United States Securities and Exchange Commission and the Canadian Securities regulatory authorities today, Thursday, March 26, 2020 at 9:00 a.m. ET.

Conference Call Details:

IntelGenx will host a conference call to discuss these 2019 fourth quarter and full year financial results on Friday, March 27, 2020 at 8:30 a.m. ET. The dial-in number for the conference call is (833) 231-8269 (Canada and United States) or (647) 689-4114 (International), conference ID 5685777. The call will be also be webcast live and archived for twelve months at www.intelgenx.com.

On March 26, 2020 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported that it has joined The Leukemia & Lymphoma Society (LLS) in the groundbreaking, collaborative Beat AML Master Clinical Trial for newly diagnosed patients 60 years of age or older with acute myeloid leukemia (AML) (Press release, Tolero Pharmaceuticals, MAR 26, 2020, View Source;lymphoma-societys-groundbreaking-beat-aml-master-clinical-trial-for-patients-with-acute-myeloid-leukemia-301030080.html [SID1234555888]). Tolero’s investigational agent, dubermatinib (TP-0903), an AXL receptor tyrosine kinase (RTK) inhibitor has been selected for a new arm in the trial for patients with TP53 mutations and/or complex karyotype.

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AML is one of the deadliest blood cancers and the second most diagnosed type of leukemia in the U.S.1 Although there have been recent advances in the treatment of AML, for patients with certain types of mutations, prognosis and responsiveness to therapy remains poor.2 The Beat AML Master Clinical Trial aims to leverage the expertise of functional genomic technologies and pharmaceutical collaborators, using a personalized medicine approach to accelerate research findings and ultimately improve outcomes for AML patients. Patients with TP53 mutations have few effective treatment options as their response rate to chemotherapy is poor and long-term survival after stem cell transplant is rare.3 The incidence of TP53 mutations in AML has been reported to be between 5 and 19 percent of patients.4,5,6,7,8

"Tolero Pharmaceuticals is proud to have been selected to join The Leukemia & Lymphoma Society in its efforts to apply a precision medicine approach toward fighting acute myeloid leukemia," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "The Beat AML Master Clinical Trial provides us a unique opportunity to contribute to the advancement of science in AML and evaluate the potential of dubermatinib in a patient group which has a poor prognosis and limited treatment options."

In the Phase 1b/2 study, dubermatinib in combination with decitabine will be evaluated in patients 60 years or older with newly diagnosed AML who have TP53 mutations and/or complex karyotype. The primary objectives of the study are to determine the safety and maximum tolerated dose of dubermatinib in combination with decitabine and evaluate the composite complete response rate. Secondary objectives of the study include overall survival and proportion of patients transitioning to allogeneic stem cell transplantation.

"We believe the Beat AML Master Clinical Trial is changing the treatment paradigm for AML as well as for clinical trials more broadly across cancer types," said Amy Burd, Ph.D., Vice President of Research Strategy, The Leukemia & Lymphoma Society. "Through this trial, we have taken a tailored approach to treatment based on patients’ unique genomic profile, with the ultimate goal of identifying safe and effective targeted therapies for patients who previously had limited options. LLS is pleased that Tolero Pharmaceuticals is joining this unprecedented collaboration of top cancer centers and scientists, several top pharmaceutical companies, the U.S. Food and Drug Administration and a leading-edge genomics company to bring novel targeted therapies to patients faster."

The trial is being conducted at several leading cancer centers across the United States.

About dubermatinib (TP-0903)

Dubermatinib is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor under evaluation in a Phase 1/2 study in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (NCT03572634) and a Phase 1a/b study in patients with advanced solid tumors (NCT02729298). Tolero is exploring parallel clinical development paths for dubermatinib in both solid and hematologic malignancies.

About AXL Kinase

AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers.9 It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.10