On November 4, 2019 Harbour BioMed (HBM) reported the start of the first clinical trial of its next-generation fully human anti-CTLA-4 antibody (HBM4003) for the treatment of patients with advanced solid tumors (Press release, Harbour BioMed, NOV 4, 2019, View Source [SID1234550228]). This trial is the first with a fully human antibody based on heavy chain only antibody technology (HCAb). HBM4003 has shown potential for increased anti-tumor activity based on enhanced antibody dependent cell toxicity (ADCC) mediated Treg depletion and a favorable safety profile resulting from reduced half-life.

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In preclinical studies, HBM4003 demonstrated potent anti-tumor activity with much lower systemic drug exposure, suggesting a potentially significant improvement in its therapeutic profile. HBM presented preclinical study results of HBM4003 in April 2019 at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The trial is design led to assess the safety, pharmacokinetic profile and preliminary anti-tumor activity of HBM4003 in patients with advanced solid tumors.

"HBM4003, based on our proprietary human HCAb platform, underscores the potential for heavy chain only antibodies in developing the next-generation of immuno-oncology therapeutics for patients," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "This study, being conducted in Australia, is the first part of a global development program, with US and China clinical trials — including combination studies — expected to begin in the near future." Dr. Wang added, "HBM is rapidly building its pipeline, with HBM4003 advancing to the clinic in less than three years and with additional mono- and bi-specific antibodies against various targets in pre-clinical development."

CTLA-4 is one of the major negative regulators of T-cell responses. Anti-CTLA-4 antibodies are immune checkpoint inhibitors with proven value in cancer immunotherapy by increasing T-cell activity to attack tumor cells. Despite demonstrated efficacy, their safety profiles have been a barrier to broader application as both mono- and combination therapies. Preclinical studies have shown that HBM4003’s immune stimulatory activity is driven by two mechanisms: depletion of immune suppressing Treg through enhanced ADCC and; inhibition of negative signaling from the interaction of CTLA-4 with the co-stimulatory molecule B7.

"Advanced solid tumors including melanoma remain a major challenge despite improvements in the standard of care," said Prof. Paul de Souza, Dean of Medicine at the University of Wollongong Australia, and a principal investigator for this study. "Preclinical studies of HBM4003 have shown great potential. This trial provides the first opportunity to evaluate how this promising compound will perform in the treatment of solid tumors."

About Heavy Chain Only Antibodies (HCAb)

Heavy-chain only antibodies consist only of two heavy chains; they lack the two light chains usually found in traditional antibodies. HCAb’s are smaller than conventional antibodies, potentially allowing for increased tissue penetration. These antibodies also maintain IgG-like pharmacokinetic properties and immune activation (Fc) functions. HCAbs can bind antigens despite having only VH domains and have shown similar specificity to regular antibodies.

HBM’s HCAbs, which are generated by its fully human transgenic mouse platform, further enable the design of versatile formats of antibodies capable of addressing different mechanisms of action and use in different applications. HCAbs are naturally generated human antibodies against desired targets; thus there is no need for humanization to reduce immunogenicity.

On November 4, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported its financial and operational results for the third quarter ended September 30, 2019 (Press release, Sierra Oncology, NOV 4, 2019, View Source [SID1234550244]).

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"During the third quarter, we continued to prepare for the launch of the MOMENTUM Phase 3 clinical trial, which is expected to occur in the fourth quarter of 2019. Data that will be generated from this trial, along with data from more than 800 myelofibrosis patients previously treated with momelotinib, many of them durably benefiting for several years of treatment, will form the basis of our planned regulatory submissions for this drug," said Dr. Nick Glover, President and CEO of Sierra Oncology. "If ultimately approved, momelotinib could represent a significant addition to the limited number of therapeutics available to patients with myelofibrosis, and potentially become the first therapeutic capable of improving anemia in these patients rather than exacerbating it, while also providing meaningful and long-lasting symptom and spleen benefits."

Sierra’s pipeline also includes a portfolio of DNA Damage Response (DDR) assets, SRA737 (Chk1 inhibitor) and SRA141 (Cdc7 inhibitor). Sierra has previously announced plans to prioritize its resources on the development of momelotinib and has launched a campaign exploring non-dilutive strategic options to support the future continued development of these other drug candidates.

About the MOMENTUM Phase 3 Clinical Trial for Patients with Myelofibrosis:

Sierra plans to launch the MOMENTUM Phase 3 clinical trial in the fourth quarter of 2019. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic and anemic, and who have been treated previously with a JAK inhibitor. Patients will be randomized 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO (Free ESMO Whitepaper) guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.

The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; p-value < 0.05).

Secondary and exploratory endpoints include:

Transfusion Independence (TI) rate at Week 24 (key secondary: >90% powered; p-value < 0.05),
Splenic response rate (SRR) at Week 24 (>90% powered; p-value < 0.05),
Duration of TSS response to Week 48,
Other measures of anemia benefit, including Transfusion Dependence response rate and various measures of cumulative transfusion burden,
Patient Reported Outcome measures of fatigue and physical function.
Dr. Srdan Verstovsek, MD, PhD, Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, has been named Chief Investigator of the MOMENTUM Phase 3 trial.

The FDA has granted Fast Track designation to momelotinib for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor.

Third Quarter 2019 Financial Results (all amounts reported in U.S. currency)

Research and development expenses were $10.1 million for the three months ended September 30, 2019, compared to $12.9 million for the three months ended September 30, 2018. The decrease was due to a $3.0 million upfront fee paid to Gilead to acquire momelotinib in the third quarter of 2018 and decreases in SRA737 and SRA141 costs, including a $2.4 million decrease in clinical trial costs primarily related to SRA737, a $1.4 million decrease in third-party manufacturing costs, and a $0.5 million decrease in research and preclinical costs. These decreases were partially offset by costs pertaining to momelotinib including an increase of $3.9 million in clinical trial and development related costs and a $0.6 million increase in third-party manufacturing costs. Research and development expenses included non-cash stock-based compensation of $0.9 million and $1.2 million for the three months ended September 30, 2019 and 2018, respectively.

Research and development expenses were $32.0 million for the nine months ended September 30, 2019, compared to $30.0 million for the nine months ended September 30, 2018. The increase was primarily due to costs related to momelotinib including a $8.2 million increase in clinical trial and development costs, a $1.9 million increase in third-party manufacturing costs and a $2.1 million increase in personnel-related and allocated overhead costs. These increases were partially offset by a $3.0 million upfront fee paid to Gilead to acquire momelotinib in the third quarter of 2018 and decreases in SRA737 and SRA141 costs, including a $3.6 million decrease in third-party manufacturing costs, a $2.4 million decrease in clinical trial costs primarily related to SRA737, and a $1.3 million decrease in research and preclinical costs. Research and development expenses included non-cash stock-based compensation of $3.3 million for the nine months ended September 30, 2019 and 2018.

General and administrative expenses were $3.1 million for both the three months ended September 30, 2019 and 2018. General and administrative expenses included non-cash stock-based compensation of $0.4 million and $0.7 million for the three months ended September 30, 2019 and 2018, respectively.

General and administrative expenses were $10.0 million for the nine months ended September 30, 2019, compared to $10.7 million for the nine months ended September 30, 2018. This decrease was due to decreases in personnel-related and allocated overhead costs of $0.3 million, professional fees of $0.2 million and business development related costs of $0.2 million. General and administrative expenses included non-cash stock-based compensation of $1.5 million and $1.8 million for the nine months ended September 30, 2019 and 2018, respectively.

For the three months ended September 30, 2019, Sierra incurred a net loss of $12.9 million compared to a net loss of $15.6 million for the three months ended September 30, 2018. For the nine months ended September 30, 2019, Sierra incurred a net loss of $40.8 million compared to a net loss of $39.1 million for the nine months ended September 30, 2018.

Cash and cash equivalents totaled $67.7 million as of September 30, 2019, compared to $106.0 million as of December 31, 2018. At September 30, 2019, there were 74,688,283 shares of common stock issued and outstanding, an additional 13,222,900 issuable upon exercise of stock options and warrants, and a term loan of $5.0 million.

On November 4, 2019 PhoreMost Limited, the UK-based biopharmaceutical company dedicated to drugging ‘undruggable’ disease targets, and Sentinel Oncology, reported an expansion of their collaboration to accelerate the progression of SOL686, a novel allosteric Polo-like kinase 1 (PLK1) inhibitor through preclinical development and IND enabling studies for the treatment of Glioma (Press release, PhoreMost, NOV 4, 2019, View Source [SID1234550261]).

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Mitotic PLKs are widely recognised as playing crucial roles in disease causing pathways, including K-Ras mutant cancers. Traditional approaches to drugging PLK enzymes have focused on targeting their active site; however this tactic has been hindered by toxicity-associated adverse events. Sentinel Oncology’s allosteric PLK1 inhibitor takes the novel approach of targeting the Polo-box domain (PBD) of the PLKs, thereby aiming to mitigate adverse events seen by active site inhibitors.

The programme has demonstrated a promising combination of specific drug-like properties, mode of action and target validation data obtained so far. Originating from the laboratory of Prof Ashok Venkitaraman at the University of Cambridge, PhoreMost subsequently developed the lead chemical series. Sentinel Oncology then optimised drug-like properties for the series and guided therapeutic positioning. Both PhoreMost and Sentinel Oncology received funding from Innovate UK for the drug discovery programme.

Dr Chris Torrance, CEO of PhoreMost, said: "We are delighted to deepen our long-standing association with Sentinel Oncology, and excited to be progressing this drug discovery programme towards the clinic. This lead compound exemplifies the value of PhoreMost’s strategy to use functional protein-protein interactions to drive the development of novel therapies, and to capitalise on its SITESEEKER platform to change the model of drug discovery through innovation, strategic partnerships and collaboration."

Robert Boyle, CEO of Sentinel Oncology, commented: "We are very excited about the prospects for this programme, and to be collaborating with PhoreMost to advance our allosteric PLK1 inhibitor. The programme adds to our NeuroOncology pipeline, has started formal preclinical studies and is well positioned to enter clinical development as a glioma treatment by 2021."

On November 4, 2019 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics targeting infectious diseases and cancers based on its proprietary arenavirus platform, reported that it will announce financial results for the third quarter ended September 30, 2019 on Tuesday, November 12, 2019, after the NASDAQ market close (Press release, Hookipa Pharma, NOV 4, 2019, View Source [SID1234553431]).

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The Company will not be conducting a conference call in conjunction with this earnings release. Until otherwise noted, the Company will only conduct an earnings conference call in conjunction with its fourth quarter earnings releases.

On November 4, 2019 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported it has initiated its compassionate use program for Namodenoson in the treatment of hepatocellular cancer (HCC), the most common form of liver cancer (Press release, Can-Fite BioPharma, NOV 4, 2019, View Source [SID1234550208]). Can-Fite’s compassionate use program has enrolled and started treating patients. The compassionate use program, which enables liver cancer patients not enrolled in Can-Fite’s clinical study to be treated with Namodenoson, is being administered by Dr. Salomon Stemmer, the Principal Investigator of the Company’s prior Phase II liver cancer study, and Professor at the Institute of Oncology, Rabin Medical Center, Israel.

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Compassionate use allows doctors and their patients the option of early access to investigational new drugs, under closely controlled and monitored circumstances, when a patient who is facing serious illness has exhausted all available treatment options.

Can-Fite’s completed Phase II liver cancer study found that Namodenoson increased overall survival in HCC patients with Child Pugh B7 (CPB7), the largest subpopulation of the study, as compared to placebo, even though the trial did not meet its primary endpoint. The Company recently completed a successful End-of-Phase II meeting with the U.S. Food and Drug Administration (FDA), in which the FDA agreed with Can-Fite’s proposed pivotal Phase III trial design to support a New Drug Application (NDA) submission and approval of Namodenoson in the treatment of HCC.

We are grateful to Dr. Stemmer for leading this compassionate use program, making Namodenoson available to patients who have exhausted all other treatment options. Based on the encouraging results of our recent Phase II trial, in which Namodenoson demonstrated clinical benefits in patients with underlying CPB7 cirrhosis, Can-Fite is committed to providing Namodenoson to fulfill the unmet medical need in this population," stated Can-Fite CEO Dr. Pnina Fishman.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated as a second line treatment for hepatocellular carcinoma, with a recently completed Phase II trial and planned Phase III trial in this indication. The drug is currently in an ongoing Phase II trial as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.