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Millendo Therapeutics Reports Third Quarter 2020 Operating and Financial Results

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.

Exicure Presents Positive Clinical Data with Cavrotolimod at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting

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]).

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.

Ikena Oncology to Present New Preclinical Data on AHR Antagonist IK-175 at the Society for Immunotherapy of Cancer’s 2020 Annual Meeting

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.

"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.

Istari Oncology Presents Positive Data from Phase 1 Study of PVSRIPO in Patients with Unresectable Treatment Refractory Melanoma at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting

On November 9, 2020 Istari Oncology, Inc., a clinical-stage biotechnology company, reported Phase 1 clinical data of its lead product candidate, PVSRIPO, for the treatment of patients with anti-PD-1 refractory melanoma at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting being held virtually from November 9-14, 2020 (Press release, Istari Oncology, NOV 9, 2020, View Source [SID1234570533]).

PVSRIPO is a novel immunotherapy consisting of a non-neurovirulent rhinovirus: poliovirus chimera that activates innate and adaptive immunity to facilitate a targeted anti-tumor immune response. Among the 6 patients who received three PVSRIPO injections (maximum number administered, separated by 21 days) without any other concomitant therapy, the overall response rate was 67% (4/6), suggesting that PVSRIPO was able to initiate or rekindle responses in patients who have failed anti-PD-1 therapy. Responses in both injected and uninjected tumors (e.g. an abscopal response) were observed.

"There is a growing population of anti-PD1 refractory patients with unresectable melanoma who have no good treatment options available to them," said Georgia Beasley, MD, Principal Investigator of the Phase 1 study at Duke University. "We are excited and encouraged by the preliminary results observed in our patients with advanced melanoma, refractory to anti-PD-1 and BRAF/MEK therapy. PVSRIPO was also very well tolerated in this advanced patient population, with no serious or dose limiting toxicities."

"We are enthusiastic about these results, and their implications regarding the therapeutic potential of PVSRIPO," said W. Garrett Nichols, MD, MS, Chief Medical Officer at Istari Oncology. "PVSRIPO appears uniquely capable of engaging both innate and adaptive immune responses to generate antitumor immunity. As we move ahead into Phase 2 studies in patients with advanced unresectable melanoma who have failed anti-PD-1 therapy, we believe that the potential for PVSRIPO to generate an abscopal response in injected and non-injected tumors may vastly expand the addressable therapeutic population and improve patient prognosis. We look forward to further evaluating PVSRIPO in both this indication and other solid tumor types, as well as in our other ongoing trials in glioblastoma."

The Phase 1 open-label trial (clinicaltrials.gov NCT03712358) enrolled 12 patients with unresectable and/or metastatic melanoma (American Joint Committee on Cancer stage IIIB, IIIC, or IV), who failed ≥1 anti-PD-1-based regimen; patients with BRAFᵛ⁶⁰⁰ mutations also failed ≥1 BRAF-targeted therapy. The primary objective of the Phase 1 study was to evaluate the safety and tolerability and explore the efficacy and immune activation of PVSRIPO in patients with advanced melanoma.

The data showed intratumoral PVSRIPO was well tolerated (all adverse events grade 1 or 2), with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs). There was no evidence of viral spread from the intratumoral inoculation site; pre-existing anti-poliovirus immunity and CD155 targeting are the likely mechanisms responsible for restricting viral spread and off-target/systemic immune related AEs.

Among the 12 treated patients, 4 (33%) met criteria for overall response rate (ORR) per immune-related response criteria, including 4/6 (67%) who received 3 injections. Pathologic complete response was observed in 2 of 4 (50%) patients with in-transit disease, showing evidence of abscopal response. Following the study’s completion, the majority of patients received additional immune checkpoint inhibitor (ICI)-based therapy and 6 out of 12 patients (50%) remained progression free at the data cutoff.

Collectively, these data suggest that PVSRIPO holds promise in anti-PD-1 refractory melanoma and further evaluation and in combination with anti-PD-1 therapy is warranted. As such, a protocol amendment exploring PVSRIPO treatment in more lesions per treatment cycle is ongoing, and the LUMINOS-102 Phase 2 study evaluating the safety and efficacy of PVSRIPO with and without anti-PD-1 therapy in the advanced anti-PD-1 refractory melanoma population is initiating; see NCT04577807 at clinicaltrials.gov for more information.

Details of Istari poster presentation:
Title: (#) A Phase I Trial of Intratumoral PVSRIPO in Patients with Unresectable Treatment Refractory Melanoma
Abstract Authors: Georgia M. Beasley, MD, MHs, Nellie E. Farrow, MD, Karenia Landa, MD, Maria Angelica Seilm, MD, Sin-Ho Jung, PhD, Darell D. Bigner, MD, PhD, Andrea True Kelly, Ph, Smita Nair, Ph, Matthias Gromeier, MD, April Salama, MD
Presentation times: Thursday, Nov. 12 from 4:50–5:20 p.m. EST and Saturday, Nov. 14 from 1–1:30 p.m. EST
Location: Virtual Poster Hall

About PVSRIPO

PVSRIPO is a virus based on the live attenuated Sabin type 1 polio vaccine that has been genetically modified for safety. Unlike other viral immunotherapies, PVSRIPO has a distinct target (the poliovirus receptor CD155), which is widely expressed in neoplastic cells of most solid tumors. Via CD155, PVSRIPO targets tumors with two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) engaging innate and adaptive antitumor immune responses via sublethal infection of antigen presenting cells in the tumor, which unleashes an inflammatory cascade resulting in sustained systemic antitumor immunity. PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma.

About Melanoma

There are estimated to be over 12,000 new and recurrent cases of advanced, unresectable melanoma diagnosed in the U.S. each year, and around 7,000 deaths. While immune checkpoint inhibitors have dramatically improved the outlook for advanced melanoma patients today, most patients treated with these immunotherapies are either primary non-responders or eventually develop immune-refractory progressive disease and require additional therapy.

Sensei Biotherapeutics Presents Additional Data from Phase 1/2 Clinical Trial of SNS-301 at the Society for Immunotherapy of Cancer (SITC) Annual Meeting

On November 9, 2020 Sensei Biotherapeutics, Inc., a clinical-stage biopharmaceutical company developing next generation immunotherapies for the treatment of cancer and infectious diseases, reported new data from its ongoing Phase 1/2 clinical trial of SNS‑301, Sensei’s lead program from its ImmunoPhage platform, in patients with Locally Advanced Unresectable or Metastatic/Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN) (Press release, Sensei Biotherapeutics, NOV 9, 2020, View Source [SID1234570532]). The data were presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting.

"These promising new data build upon the initial safety and efficacy data for SNS-301 in patients with ASPH-positive SCCHN and provide additional confidence that SNS-301, when combined with checkpoint inhibition, has the potential to provide long-term benefit as 2nd and later line treatment for patients," said Marie-Louise Fjällskog, M.D., Ph.D., Chief Medical Officer of Sensei Biotherapeutics. "These results, including a partial response in an advanced SCCHN patient with a PD-L1 negative tumor, as well as translational data demonstrating a shift from an immune desert to an inflamed phenotype, represent a notable achievement for Sensei, further validating our unique phage-based platform approach."

The multi-center Phase 1/2 clinical trial is designed to assess the safety, efficacy and immunogenicity of SNS-301 in SCCHN patients that did not achieve tumor reductions on anti-PD-1/PD-L1 therapy alone. As of the data cutoff date of October 6, 2020, eleven patients were enrolled in the study and enrollment is ongoing. Key highlights from the poster titled "Early Safety and Efficacy of a Phase 1/2 Multi-Center Trial of SNS-301 Added to Pembrolizumab in Patients with Advanced Squamous Cell Carcinoma of the Head and Neck" are:

Disease control in 6 of 9 patients evaluable for efficacy, including:
One patient with PD-L1 negative disease achieved a partial response (PR) with a tumor reduction of 43% at week 12 and was confirmed at week 18. Immunohistochemical staining of this patient’s tumor pre- and post-treatment demonstrated clear increases in CD8 density and PD-L1 expression on CD8 T cells and macrophages. This patient also achieved a clear serological response.
One patient achieved a stable disease (SD) for more than 4 months following progressive disease (PD) after 10 months of PD-1 blockade treatment prior to study entry.
Two patients achieved SD for 36+ weeks.
Of the three patients that had PD as their best response, two had PD on single agent PD1 blockade when entering the study.
SNS-301 was well tolerated with no dose-limiting toxicities and observed adverse events (AEs) have primarily been either Grade 1 or 2 and mostly unrelated to treatment.
Nanostring analysis of tumors from patients with a partial response, stable disease, and progressive disease was generally concordant with clinical effect, including across immune parameters such Th1 markers, IFN-gamma, Granzyme B, and CD8 T cells.
In addition to the new safety and efficacy data presented today, Sensei also presented a trial-in-progress (TIP) poster describing the design of the ongoing Phase 1/2 clinical trial of SNS-301 in combination with pembrolizumab in SCCHN patients.

About SNS-301

SNS-301 is a first-in-class cancer immunotherapy designed to overcome immune tolerance and induce robust and durable antigen-specific humoral and cellular responses. It is a bio-engineered, inactivated bacteriophage virus expressing a fusion protein of native bacteriophage GPD (Glyceraldehyde-3-phosphate dehydrogenase) protein and a selected domain of aspartate β-hydroxylase (ASPH). Expression of ASPH is uniquely upregulated in more than 20 different types of cancer and expression levels in various tumors are generally inversely correlated with disease prognosis. ASPH signaling is related to cancer cell growth, cell motility and invasiveness, occurs through the Notch pathway and is implicated in the epithelial to mesenchymal transition (EMT).