On November 4, 2019 ADC Therapeutics SA, a clinical-stage oncology-focused biotechnology company pioneering the development of highly potent and targeted antibody drug conjugates (ADCs) for patients suffering from hematological malignancies and solid tumors, reported that ADCT-402 (loncastuximab tesirine) data have been published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), in a paper titled, "A Phase 1 study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (Press release, ADC Therapeutics, NOV 4, 2019, View Source [SID1234596053])."

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The Phase 1 multi-center, open-label, single-arm, dose-escalation and dose-expansion clinical trial demonstrated the significant single-agent clinical activity and manageable tolerability profile of ADCT-402 in patients with CD19-positive relapsed or refractory B-cell non-Hodgkin lymphoma who had failed or were intolerant to established therapies. The published paper includes findings from the dose-escalation part of the trial. Notably, among the 61 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were evaluable for efficacy, a 55 percent response rate was observed at doses ≥120 µg/kg. Eighty-seven of the 88 patients enrolled in the trial experienced at least one treatment-emergent adverse event (TEAE). The most common TEAEs were low blood cell counts, fatigue, liver test abnormalities, nausea, rash, shortness of breath and tissue swelling.

Brad S. Kahl, MD, Professor of Medicine at Washington University School of Medicine and lead author of the paper, said, "The first-in-human study of ADCT-402 justified its continued evaluation and identified the initial 150 µg/kg dose for the Phase 2 clinical trial. The promising clinical activity and manageable toxicities observed thus far highlight the potential utility of ADCT-402 as an off-the-shelf therapy for heavily pre-treated patients with DLBCL, a population for which a significant unmet medical need remains."

Jay Feingold, MD, PhD, Senior Vice President, Chief Medical Officer and Head of Oncology Clinical Development at ADC Therapeutics, added, "The publication of early ADCT-402 data in a peer-reviewed journal further validates the potential of our lead product candidate to become an important part of the treatment paradigm for relapsed or refractory DLBCL. With enrollment in our pivotal 145-patient Phase 2 clinical trial of ADCT-402 complete, we plan to submit a Biologics License Application to the U.S. Food and Drug Administration for accelerated approval of ADCT-402 for the treatment of relapsed or refractory DLBCL in patients who have failed two or more treatment regimens in the second half of 2020."

ADCT-402 is also being evaluated in an ongoing Phase 1b clinical trial in combination with ibrutinib for the treatment of relapsed or refractory DLBCL or mantle cell lymphoma (MCL) and a Phase 1b clinical trial in combination with durvalumab for the treatment of relapsed or refractory DLBCL, MCL and follicular lymphoma.

About ADCT-402

ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Once bound to a CD19-expressing cell, ADCT-402 is designed to be internalized by the cell, following which the warhead is released. The warhead is designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, thus disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death. CD19 is a clinically validated target for the treatment of B-cell malignancies. ADCT-402 is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (NCT03589469), a Phase 1b trial in combination with ibrutinib in patients with R/R DLBCL or mantle cell lymphoma (MCL) (NCT03684694) and a Phase 1b trial in combination with durvalumab in patients with R/R DLBCL, MCL or follicular lymphoma (NCT03685344). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of relapsed or refractory DLBCL and MCL.

On November 4, 2019 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, adoptive cell therapies1, and cancer vaccines provided a corporate update and reported financial results for the third quarter of 2019 (Press release, Agenus, NOV 4, 2019, View Source [SID1234550207]).

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"We have made solid progress this year," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "We expect clinical readouts from six separate antibody programs in 2020 as our robust pace continues. We expect to commence combo trials of our NexGen CTLA-4 with our own PD-1 this month. 2020 is expected to be an important year of data generation, substantial milestone payments and prudent collaborations for Agenus. We look forward to discussing these developments in more detail during our call and at our R&D day on November 15th."

Achievements
Delivered on partnership programs; received additional cash milestones
Received $22.5 million from Gilead as milestone payment for IND acceptances of AGEN1423 (now GS-1423), AGEN1223, & AGEN2373
CTLA-4 & PD-1 trials advance
2L cervical cancer trial designed to support BLA via accelerated pathway
Combination trial completes accrual and interim analysis
Monotherapy trial is on track to complete accrual and interim analysis by year-end
AGEN1181 (NexGen CTLA-4) trial advancing; combos with AGEN2034 (PD-1) to start
QS-21 Updates
Sales of Shingrix exceed $1Bn; eliminating HCR debt obligation and nearing milestone triggers of up to $40M
AgenTus Cell Therapy Business:
IND for AgenTus allogeneic cell therapy on track by year end; combos with Agenus check point antibodies planned in 2020
Partnership and private financing discussions are underway
Dr. Walter Flamenbaum appointed CEO of AgenTus
Third Quarter 2019 Financial Results

We ended the third quarter of 2019 with a cash balance of $93 million as compared to $53 million at December 31, 2018.

Cash used in operations for the quarter ended September 2019 was $28 million compared to $25 million for the same period in 2018. Cash provided by operations for the nine months ended September 2019 was $13 million as compared to cash used in operations of $95 million for the same period in 2018.

For the third quarter ended September 30, 2019, we reported net loss of $46 million or $0.33 per share compared to a net loss for same period in 2018 of $34 million, or $0.29 per share. For the nine months ended September 30, 2019, we reported a net loss of $81 million or $0.58 per share compared to a net loss for the same period in 2018 of $113 million or $1.04 per share.

During the nine months ended September 2019 we recognized revenue of $116 million which includes revenue from our transaction with Gilead and non-cash royalties earned. This compares to revenue of $30 for the nine months ended September 2018. Through the third quarter of 2019 we also recorded $30 million of non-cash interest expense due to our transaction with HCR related to the sale of future royalties.

Conference Call, Webcast and Prepared Statement Information

Date: Monday, November 4, 2019
Time: 8:30 a.m. ET
Domestic Dial-in Number: (844) 492-3727
International Dial-in Number: (412) 317-5118
Conference ID: Agenus

Live Webcast: accessible from the Company’s website at View Source or with this link View Source

A replay will be available on the Company’s website approximately two hours after the call and will remain available for 90 days.

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."