On November 9, 2020 Seven and Eight Biopharmaceuticals Inc., a clinical stage biotechnology company focused on developing proprietary novel immuno-oncology therapies to activate the immune system against cancer, reported interim Phase 1 results evaluating BDB001, its Toll-like receptor 7/8 (TLR7/8) agonist (NCT03486301), at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting to be held virtually November 9 – 14, 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting.

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"The responses seen with BDB001 in anti-PD-(L)1 refractory tumors are notable and will guide our development program in these difficult to treat tumors"

The interim Phase 1 results show that intravenous administration of BDB001 as monotherapy is well-tolerated and induces robust immune activation resulting in clinical responses in solid tumors, including deep responses in anti-PD-(L)1 refractory tumors. BDB001 is an immune modulator capable of activating dendritic cells to initiate both innate and adaptive immunity against cancer. BDB001 is a first-in-class TLR7/8 agonist delivered intravenously, allowing for broader treatment of solid tumors compared to intratumoral TLR agonists in development.

"These initial data showing that BDB001 can be safely delivered intravenously and produce clinical responses in heavily pre-treated tumors are encouraging," said Dr. Manish R. Patel, presenter of the BDB001 Phase I clinical trial abstract, and a study investigator.

"The responses seen with BDB001 in anti-PD-(L)1 refractory tumors are notable and will guide our development program in these difficult to treat tumors," said Dr. Robert H.I. Andtbacka, Chief Medical Officer, Seven and Eight Biopharma. "The potential for BDB001, as an immuno-oncology backbone, in combination with anti-PD-(L)1 therapies is currently being evaluated in several clinical trials, and early findings are promising."

"We are very excited about the clinical BDB001 monotherapy data as we advance our robust immuno-oncology pipeline in treatments beyond anti-PD-(L)1, including preclinical platform programs in TLR Ligand Antibody Conjugation," said Dr. Walter Lau, Chief Executive Officer, Seven and Eight Biopharma. "Our assets will help us expand our programs globally."

Presentation Details:

Title: BDB001, a Toll-Like Receptor 7 and 8 (TLR 7/8) agonist, can be safely administered intravenously ​and shows clinical responses in advanced solid tumors​
Abstract Authors: Manish R. Patel, Drew Rasco, Melissa Johnson, Anthony Tolcher, Lixin Li, Adam Zong, Alexander Chung, Robert H.I. Andtbacka
Abstract #: 324
Presenter: Manish R. Patel
Presentation times: November 9 – 14, 8:00 a.m. – 5:00 p.m. EST
Location: Virtual Poster Hall

The poster presentation will be available for virtual viewing at the SITC (Free SITC Whitepaper) meeting website until December 31, 2020 and will also be made available on the Company’s website at www.7and8biopharma.com.

Full abstract:

Background: TLR agonists mediate antitumor activity through dendritic cell (DC) activation. Most TLR agonists in development are administered intratumorally allowing for less than 30% of advanced solid tumor to be treated. BDB001 is an intravenously administered novel TLR7/8 agonist that activates plasmacytoid and myeloid DCs and has shown to have activity in preclinical studies. Here we report on BDB001 administration in patients with advanced solid tumors.

Methods: BDB001-101 is a Phase 1, open label, dose escalation/expansion trial of BDB001 administered intravenously weekly in patients with advanced solid tumors. The primary endpoint was safety and tolerability. Secondary endpoints included efficacy, pharmacokinetics and pharmacodynamic profiling of immune activation.

Results: Thirty-six subjects with 16 different tumor types were enrolled across 5 dose levels. Sixty seven percent were female, median age was 66 years (range, 38-88), median number of prior therapies was 4 (range, 0-12), and 61% of tumors had progressed on prior anti-PD-(L)1 therapy. BDB001 was well tolerated and a maximum tolerated dose was not reached. Eleven (30.5%) subjects had no treatment related adverse events (AEs) and the majority of AEs were Grade 1 or 2. Three (8.3%) subjects had Grade 3 AEs, including 2 with a cytokine release syndrome, both of whom were clinically stable and had symptoms fully resolved within 2 to 5 days. There were no Grade 4 or 5 AEs. The most common AEs included chills/rigor (19.4%), fever (19.4%), fatigue (11.1%), nausea (11.1%) and pruritus (11.1%). Of 32 subjects evaluable for efficacy, best overall response rate was: 6% durable partial response, 56% stable disease, 38% progressive disease, for a disease control rate of 62%. Durable responses were seen in renal cell carcinoma and non-small cell lung cancer. Interestingly, clinical activity favored subjects with tumors that had progressed on prior anti-PD-(L)1 therapy, compared to prior DNA-damaging chemotherapy, within 6 months of BDB001 initiation. Median time on treatment was 12.1 weeks (range, 3.1 – 68.0). Transcriptional profiling showed up-regulation of interferon inducible genes, activation of dendritic cells and macrophages. BDB001 also significantly increased serum levels of interferon gamma and interferon inducible protein-10 (IP-10).

Conclusions: Intravenously administered BDB001 monotherapy was well tolerated. Clinical responses were achieved, supported by BDB001-induced immune activation. Preliminary findings suggest that BDB001 is a promising therapeutic option for patients with tumors that progress on anti-PD-(L)1 therapy. BDB001 is also being evaluated in combination with pembrolizumab (anti-PD-1, NCT03486301) and with atezolizumab (anti-PD-L1, NCT04196530).

On November 9, 2020 Genialis, a leader in applied data science for the development of precision medicines, reported that it will present a poster alongside OncXerna (fka Oncologie) at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) conference (SITC 2020) (Press release, Genialis, NOV 9, 2020, View Source [SID1234570538]). The poster, titled "Development of an RNA-based Diagnostic Platform Based on the Tumor Microenvironment Dominant Biology," (Poster 257) will be discussed on Wednesday, November 11, and Friday, November 13, 2020.

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The SITC (Free SITC Whitepaper) presentation is the first scientific disclosure from the companies’ ongoing collaboration, previously announced in January 2020, to develop a state-of-the-art RNA-based biomarker platform, with this initial panel capturing the complexities of the tumor microenvironment. Today, 90 percent of patients do not have a precision medicine solution based on DNA profiling. Thorough characterization of RNA expression enables OncXerna’s panel to describe the cancer’s dominant biology to match patients to a drug whose MOA targets that biology. Genialis is optimizing algorithms for patient selection, a critical step towards developing a companion diagnostic for a given drug. The poster will highlight biomarker validations on approved therapies and application to OncXerna’s investigational clinical programs.

Genialis’ participation at SITC (Free SITC Whitepaper) is the latest in a series of milestone achievements in the last two quarters of 2020, including ongoing engagements with biopharma collaborators; updates to its precision medicine software platform; and an addition to its board of directors. More information on each of these updates can be found below:

PRECISION MEDICINE COLLABORATIONS

Throughout 2020, Genialis’s industry partners have drawn from the company’s expertise in gene expression and genome regulation to develop or discover innovative new drugs across the R&D lifecycle, from target validation to translational modeling to clinical biomarkers. Of these diverse use cases, the last piece—biomarkers that predict drug response—remains a central focal point. These partners include growth-stage biotechs, including InhibRx, Elevar and Kronos, as well as various larger pharma with deep pipelines, to academic institutions like Baylor College of Medicine’s Therapeutic Innovation Center (THINC).

ANALYTICS SOFTWARE

Genialis has also recently released an update to its proprietary software features as part of the Expressions platform to include a formal pipeline to support the analysis of data generated by the Cut-and-Run method for DNA-protein binding. This is a tool increasingly used to study transcription factors and other chromatin modifiers. Other novel methods supported on Expressions include SLAM-seq, for dissecting transcriptional dynamics, and various permutations of CLIP-seq, for assaying transcriptional processing. Genialis and Roche are also currently co-promoting their unified solution for Roche’s KAPA RNA HyperPrep Kits.

PEOPLE NEWS

In Q3 2020, Nadine Geiser, Ph.D., joined the Board of Directors. Dr. Geiser is an investment manager at Redalpine Venture partners and takes over the firm’s seat on the board. She is a formally trained scientist, studied biotechnology in Munich, Germany and Singapore before completing a Ph.D. in proteomics at ETH Zurich, Switzerland. Previously Dr. Geiser worked in Amsterdam for a corporate venture firm and in the equity research department of an investment bank in Zurich before joining Redalpine in 2019.

"To realize the potential of precision medicine, we need to better master the data that explains the biology of various diseases," said Dr. Geiser. "I’ve spent my career first in the lab researching proteomics and then investing in companies with game-changing approaches to decipher and engineer biology. Genialis’ approach to data integration, and in particular their expertise with gene expression-based models, will help the company’s therapeutic partners succeed in the clinic to help get new treatment options to patients."

INDUSTRY ADVOCACY

Genialis remained an active member of the Alliance for Artificial Intelligence in Healthcare, most recently contributing to the organization’s webinar series on the various applications of AI in both drug discovery and clinical uses. Rosengarten moderated a discussion for AAIH focusing on "Optimizing Real World Data for Therapeutic Development," and participated as a panelist for a discussion on best practices for running a "Biotech Startup in the Cloud." He also recently spoke at the AI Applications in BioPharma.

"The center of our work, while extremely technical, is all driven by getting patients better access to better medicines to treat a range of conditions. We’re tackling some really hard problems in oncology and rare disease that invariably leads to exciting innovations when we finally breakthrough," said Dr. Rosengarten. "Having the brain trust addition of Nadine to our board will complement our current team well, as she brings expertise in both analyzing the results we see in the lab and also guide us in growth with her finance background."

On November 9, 2020 Millendo Therapeutics, Inc. (Nasdaq: MLND), a clinical-stage biopharmaceutical company primarily focused on developing novel treatments for endocrine diseases with significant unmet needs, reported financial results for the quarter ended September 30, 2020 (Press release, Millendo Therapeutics, NOV 9, 2020, View Source [SID1234570536]).

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"We continue to advance MLE-301 as a potential alternative to hormone replacement therapy for the treatment of vasomotor symptoms (VMS) related to menopause, and were pleased to initiate our Phase 1 clinical trial in the 3rd quarter," said Julia C. Owens, President and Chief Executive Officer of Millendo Therapeutics. "MLE-301 is a priority program for Millendo, given the broader industry excitement around its potential to address a large unmet need, along with a refocusing of our internal pipeline efforts. With over 20 million women in the United States suffering from menopausal VMS, and with symptoms lasting on average over seven years, there is still a critical need for a treatment that has the efficacy of hormone replacement therapy without increased risks of cancer or cardiovascular disease."

Third Quarter 2020 and Recent Highlights

MLE-301 Phase 1 clinical trial initiated in 3Q20 as planned: A selective neurokinin 3 receptor (NK3R) antagonist, MLE-301, is being developed for the treatment of vasomotor symptoms (VMS), commonly known as hot flashes and night sweats, in menopausal women. The single ascending dose portion of the study, being conducted in healthy male volunteers, will determine the pharmacokinetics of MLE-301 and its pharmacodynamic profile as measured by reductions of biomarkers (luteinizing hormone, testosterone). The multiple ascending dose portion will enroll post-menopausal women, with the goal of measuring reductions in VMS frequency and severity and establishing initial clinical proof of concept. The company continues to monitor the COVID-19 pandemic closely and will provide updates pending any potential impact to trial enrollment.
Nevanimibe program for patients with congenital adrenal hyperplasia (CAH) winding down: Further investment in the development of nevanimibe as a potential treatment for CAH has ceased, and out-licensing options are being explored.
Comprehensive evaluation of strategic options continues: SVB Leerink is supporting a strategic review process to build an actionable plan leveraging the company’s assets, capital and capabilities to maximize shareholder value.
Third Quarter 2020 Financial Results

Cash Position: Cash, cash equivalents and restricted cash were $43.8 million at September 30, 2020, compared to $63.5 million at December 31, 2019.

Research and Development (R&D) Expenses: R&D expenses were $2.7 million for the third quarter 2020, as compared to $7.3 million for the same period in 2019. The decrease in R&D expenses was primarily driven by decreased spend due to discontinuing our development of the livoletide program and ceasing investing in the nevanimibe program, offset by increased spend on MLE-301.

General and Administrative (G&A) Expenses: G&A expenses were $3.4 million for the third quarter 2020, as compared to $4.4 million for the same period in 2019. The decrease in G&A expenses was primarily driven by decreased professional fees as a result of lower accounting and consulting fees incurred as compared to the prior period. Compensation and stock-based compensation decreased as a result of a decrease in our general and administrative headcount and changes to compensation arrangements.

Net Loss: The company’s net loss for the quarter ended September 30, 2020 was $6.4 million as compared to $11.6 million for the same period in 2019.

2020 Financial Guidance

Millendo expects that its cash, cash equivalents and restricted cash will support its current development and operational plans into 2022.

About MLE-301

MLE-301 is a neurokinin 3 receptor (NK3R) antagonist that is being developed as a potential treatment of vasomotor symptoms (VMS), commonly known as hot flashes and night sweats, in menopausal women. NK3R plays a key role in regulating the activity of KNDy (kisspeptin/NKB/dynorphin) neurons, which has been shown to participate in the generation of VMS. By inhibiting the NK3R signaling on the KNDy neurons and potentially other NK3R-expressing neurons that propagate heat dissipation signals through the hypothalamus, MLE-301 aims to reduce the effects of hyperactive KNDy neurons and thereby decrease the frequency and severity of vasomotor symptoms.

On November 9, 2020 Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing proprietary spherical nucleic acid (SNA) technology, reported the presentation of updated Phase 1b data from the ongoing Phase 1b/2 clinical trial evaluating intratumoral cavrotolimod (AST-008), the Company’s SNA-enabled TLR9 agonist, in combination with the anti-PD-1 therapies pembrolizumab (KEYTRUDA) or cemiplimab (LIBTAYO), in patients with Merkel cell carcinoma, cutaneous squamous cell carcinoma, and other advanced solid tumors (NCT03684785) (Press release, Exicure, NOV 9, 2020, View Source [SID1234570535]).

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The Phase 1b dose-escalation stage was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of cavrotolimod alone and in combination with pembrolizumab, and to identify a recommended Phase 2 dose. Cavrotolimod was dosed intratumorally once weekly for 8 weeks and subsequently once every 3 weeks. Following an initial cavrotolimod monotherapy period, pembrolizumab was initiated at week 3 and dosed in combination with cavrotolimod once every 3 weeks. The Phase 1b stage enrolled patients with locally advanced or metastatic melanoma (n=10), Merkel cell carcinoma (n=5), cutaneous squamous cell carcinoma (n=2), head and neck squamous cell carcinoma (n=2), and leiomyosarcoma (n=1).

Updated data from the Phase 1b stage demonstrated that the combination of cavrotolimod and pembrolizumab continued to be well tolerated, with a confirmed overall response rate (ORR) of 21% (4/19 patients) according to RECIST v1.1 criteria. The combination immunotherapy regimen induced durable and systemic anti-tumor responses in patients with advanced solid tumors who previously progressed on anti-PD-1 therapy. At the time of enrollment in the clinical trial, 85% of patients were experiencing progressive disease despite treatment with PD-1 blockade and 65% of patients had been treated with 2 or more lines of systemic therapy.

Highlights from the Phase 1b Dose-Escalation Stage

– The RECIST-confirmed ORR was 21% (4/19 patients) overall in the Phase 1b dose-escalation stage, reflecting 1 complete response and 3 partial responses.

– In the highest cavrotolimod dose cohort (32 mg), which was selected as the Phase 2 dose, the RECIST-confirmed ORR was 33% (2/6 patients).

– Responses were durable and ongoing at the time of data analysis, with progression-free survival exceeding 6 months in all 4 responders and 16 months in 2 responders.

– 85% of patients overall (17/20 patients) and 75% of responders (3/4) were progressing on anti-PD-1 therapy at the time of trial enrollment.

– Systemic (abscopal) effects were observed, with shrinkage of regional or distant noninjected tumors.

– The majority (98%) of treatment-related adverse events were grade 1 or grade 2. No dose-limiting toxicities and no treatment-related serious adverse events were reported in the Phase 1b stage. The most common adverse events were flu-like symptoms and injection site reactions, consistent with other adverse events experienced with local and systemic immune activation associated with TLR9 agonism.

Details of the poster presentation are as follows:

Title: Safety and preliminary efficacy of intratumoral cavrotolimod (AST-008), a spherical nucleic acid TLR9 agonist, in combination with pembrolizumab in patients with advanced solid tumors

Authors: Steven J. O’Day, Cesar A. Perez, Trisha M. Wise-Draper, Glenn J. Hanna, Shailender Bhatia, Ciara M. Kelly, Theresa M. Medina, Douglas E. Laux, Adil Daud, Sunandana Chandra, Montaser Shaheen, Ling Gao, Melissa A. Burgess, Leonel Hernandez-Aya, Emil M. deGoma, Weston L. Daniel, Douglas E. Feltner, Laurel Sindelar, Robert E. Michel, Alice S. Bexon, Martin Bexon, and Mohammed M. Milhem

Poster/Abstract Number: 423

The abstract and poster will be available on the SITC (Free SITC Whitepaper) website once the conference begins on Monday, November 9 at 8:00 a.m. EST. The poster will also be made available on the Exicure website.

Live Q&A will take place Wednesday, November 11 from 5:15–5:45 p.m. EST and Friday, November 13 from 4:40–5:10 p.m. EST.

On November 9, 2020 Ikena Oncology, Inc. ("Ikena"), a clinical-stage, biotechnology company that discovers and develops patient-directed, biomarker-driven therapies, reported that a poster presentation will take place at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 2020 Annual Meeting, taking place virtually November 9-14, 2020 (Press release, Ikena Oncology, NOV 9, 2020, View Source [SID1234570534]). New preclinical data will be presented for IK-175, the Company’s selective oral aryl hydrocarbon receptor (AHR) antagonist currently in Phase 1 studies.

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"Activated AHR prevents immune recognition in a range of cancers by modulating both innate and adaptive immunity. This attribute makes AHR a compelling drug target, especially in patients who do not fully benefit from standard-of-care, including checkpoint inhibitors," said Sergio Santillana, M.D., M.Sc., Chief Medical Officer of Ikena Oncology. "The preclinical data presented at SITC (Free SITC Whitepaper) is important because they demonstrate that IK-175 is an orally active AHR antagonist that inhibits tumor growth and reverses immune suppression in preclinical models, providing the rationale for studying this agent in humans. The ongoing Phase 1 study evaluating IK-175 in patients with advanced solid tumors and urothelial carcinoma is progressing well and we look forward to reporting initial results as it matures."

Summary of Preclinical Research

In this study, IK-175 inhibited AHR activity in rodent and human cancer cell lines as well as human and nonhuman primate primary immune cells, with concentration dependent effects on AHR target gene expression and cytokine release. Orally administered IK-175 dose-dependently demonstrated pharmacodynamic modulation in vivo in mice. Treatment led to an increase in proinflammatory cytokines and CD8+ T-cells in tumor draining lymph nodes, as well as an increase in proinflammatory macrophages and a decrease in Tregs in tumors. IK-175 alone and in combination with an anti-PD-1 antibody demonstrated significant antitumor activity in multiple syngeneic mouse cancer models. In addition, IK-175 in combination with liposomal doxorubicin demonstrated antitumor activity in syngeneic mouse cancer models.

Collectively, these results demonstrate that IK-175 is an orally active AHR antagonist that inhibits tumor growth and reverses immune suppression in mouse tumors models. These data provide rationale for targeting AHR in humans with cancer. IK-175 is currently being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors and urothelial carcinoma (NCT04200963). Ikena intends to evaluate the anti-tumor activity of IK-175 as a single agent, and in combination with other therapies, in cancers with activated AHR.

Details for the SITC (Free SITC Whitepaper) 2020 presentation are as follows:

Title: Discovery of clinical candidate IK-175, a selective orally active AHR antagonist
Presenter: Karen McGovern, Ikena Oncology
Session: Virtual Poster Hall
Poster #: 448
Date and time: Wednesday, November 11, 2020 to Saturday, November 14, 2020 from 9:00 am to 5:00 pm ET

About IK-175

IK-175 is a selective oral AHR antagonist which prevents AHR-modulated tumor promotion through its influence on both the tumor and the immune system. IK-175 is currently being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors and urothelial carcinoma (NCT04200963). Ikena is employing a multi-assay AHR activation biomarker strategy to select lead cancer indications and enable prospective selection of patients believed most likely to benefit from IK-175. Two patents with claims directed to IK-175 have been issued by the United States Patent and Trademark Office. Ikena’s IK-175 program is the subject of a global strategic collaboration with Bristol Myers Squibb. Ikena is responsible for research and development activities for IK-175 through Phase 1b. Bristol Myers Squibb is then eligible to globally license IK-175 and would be responsible for further development and commercialization.