On November 11, 2019 Akeso Biopharma ("Akeso") reported that results of phase 1 study of its first-in-class bispecific drug candidate AK104, in patients with advanced solid tumors in 2019 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC") (Press release, Akeso Biopharma, NOV 11, 2019, View Source [SID1234550866]). AK104 is a novel, tetrameric bispecific antibody targeting both PD-1 and CTLA-4.

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Dr. Ben Markman, MBBS(Hons) FRACP from Monash Health, Australia gave the oral presentation at the SITC (Free SITC Whitepaper) Single Agent Phase 1 Clinical Trials Session chaired by Dr. Helen Chen from National Cancer Institute and Dr. Naiyer Rizvi of Columbia University Medical Center. "AK104 has shown excellent tolerability so far with encouraging signs of anti-tumor activity. I very much look forward to tracking the further development of this exciting tetrameric bispecific antibody targeting PD1 and CTLA4", commented Dr. Ben Markman.

Updated results from Phase 1a study (NCT03261011):

AK104 showed encouraging anti-tumor activities across a range of tumor types.
– Among 25 PD-1/L1 naïve response-evaluable patients administrated with ≥ 2 mg/kg AK104, ORR: 24% ( DoR ranging from 2+ to 11.1+ months); DCR: 44%.
AK104 had an acceptable safety profile. Early data suggested that AK104 may have improved tolerance compared with the combination of a PD-1 inhibitor and CTLA-4 inhibitor.
– With 55 patients enrolled, most common treatment-related AE includes rash, infusion reaction, nausea, and fatigue.
– ≥ Grade 3 treatment-related AE (TRAE) rate was 11% with only one Grade 4 event reported. Grade 3 immune-related AE (irAE) rate was 3.6%.
AK104 commenced a Phase 1a study in patients with advanced solid tumors in Australia in October 2017, received NMPA IND approval in May 2018, and IND approval from the FDA in April 2019. AK104 is currently in Phase Ib/II clinical trials globally for multiple indications and has exhibited promising clinical safety and efficacy results in monotherapy and combination therapy.

Details of the material used in oral presentation can be found at SITC (Free SITC Whitepaper) website.

About AK104

AK104 is a potential next-generation, first-in-class humanized IgG1 tetrameric bi-specific antibody drug candidate that is based on Akeso’s proprietary "TETRABODY" technology and simultaneously targets two immune checkpoint molecules: PD-1 and CTLA-4. PD-1 and CTLA-4 co-express in tumor infiltrating lymphocytes (TILs), but not in normal peripheral tissues. AK104 is in a tetrameric form, which is designed to bind to PD-1 and CTLA-4 simultaneously to achieve the efficacy of PD-1 and CTLA-4 combination blockade with lowered toxicity.

On November 11, 2019 A quality expert and lead oncology hospitalist from the Dana-Farber Cancer Institute in Boston – the principal teaching affiliate for Harvard Medical School and one of the nation’s highest-ranked cancer hospitals – is the new Chief Medical Officer of University Hospitals Seidman Cancer Center (Press release, University Hospitals, NOV 11, 2019, View Source [SID1234550865]).

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Brett Glotzbecker, MD, brings 15 years of experience at Brigham and Women’s Hospital/Dana-Farber Cancer Institute. As an assistant professor at Harvard Medical School, Dr. Glotzbecker was honored with awards from the Dana-Farber/Harvard Cancer Center for excellence in teaching and quality achievement. She had been the principal investigator on multiple funded projects, most recently to compare outcomes for hematopoietic cell transplant patients and another to improve communication toward a more efficient discharge process.

"The UH Seidman Cancer Center family is so fortunate to have attracted a physician leader of Dr. Glotzbecker’s stature. Her expertise in patient experience, quality and clinical care delivery will help us achieve our stated goal of being the US leader in value based cancer care," said Theodoros N. Teknos, MD, President and Scientific Director of UH Seidman Cancer Center.

Dr. Glotzbecker received her medical degree and a bachelor’s degree in bioengineering from the University of Pennsylvania in Philadelphia. She completed her residency in internal medicine and her clinical/research fellowship in hematology and medical oncology from Beth Israel Deaconess Medical Center in Boston.

As Chief Medical Officer, Dr. Glotzbecker will oversee quality and the patient experience for all disease teams and tumor conferences, providing focused leadership for achieving all key certifications. She will be the senior physician liaison for cancer practitioners throughout the system. Dr. Glotzbecker will work closely with Nursing, Medical Staff and Quality. As a physician of University Hospitals Medical Group and the Department of Medicine Division of Hematology and Oncology, Dr. Glotzbecker also will provide inpatient clinical care or other care, such as consults, tumor boards and call coverage.

On November 11, 2019 Replimune Group Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported financial results for its second fiscal quarter, ended September 30, 2019, and provided a corporate update (Press release, Replimune, NOV 11, 2019, View Source [SID1234550863]).

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"It has been a very productive and exciting period for Replimune," said Robert Coffin, Ph.D., President and CEO of Replimune. "The highlight was the SITC (Free SITC Whitepaper) 2019 presentation of RP1 clinical data which confirmed the expected mechanism of action, initial safety profile, and evidence of anti-tumor efficacy providing strong support for our ongoing and expanded programs in CSCC and melanoma. Based directly on this data, the decision was taken to conduct a new clinical trial in solid organ transplant patients with CSCC and in melanoma patients who are refractory to prior treatment with anti-PD1 directed therapy. We were also very pleased to have initiated the first clinical trial of our second clinical product candidate, RP2. Overall we are thrilled with Replimune’s progress in the quarter and excited for the future as we continue to execute upon our mission to make our oncolytic immuno-gene therapies a cornerstone of cancer treatment."

Recent Business Highlights and Upcoming Events

RP1 – Presented initial data from the Phase 1/2 clinical trial of RP1 alone and in combination with Opdivo at SITC (Free SITC Whitepaper) 2019. The data presented demonstrated that RP1 used alone and in combination with Opdivo is well tolerated and showed clear anti-tumor efficacy in target tumor types that provides strong support for Replimune’s ongoing and planned development programs in melanoma and CSCC. This clinical trial is being conducted under a clinical trial collaboration and agreement with Bristol Myers Squibb (BMS) for the supply of Opdivo.

RP1 – Initiated the registration-directed Phase 2 clinical trial of RP1 in combination with Libtayo in CSCC. This multi-center, randomized, controlled clinical trial is intended to enroll approximately 240 patients with CSCC. The clinical trial’s primary objective is to compare the response rate following treatment with RP1 in combination with Libtayo to the response rate achieved with Libtayo alone. Libtayo is an FDA-approved anti-PD-1 therapy developed by Regeneron and Sanofi for the treatment of patients with metastatic or locally-advanced CSCC who are not candidates for curative surgery or radiation. This clinical trial is being conducted under the Company’s collaboration agreement with Regeneron, whereby the Company and Regeneron will split equally development and supply costs. Recruitment into this clinical trial is expected to take approximately 18 to 24 months.

RP1 – Recruitment ongoing in the Phase 2 part of the Phase 1/2 trial of RP1 in combination with Opdivo. The Phase 2 part of the clinical trial is currently enrolling 30-patient cohorts of patients with melanoma, non-melanoma skin cancers, metastatic bladder cancer and microsatellite instability high (MSI-H) tumors.

RP1 – New clinical trial planned of RP1 as monotherapy in organ transplant recipients with CSCC. CSCC represents a significant unmet medical need in organ transplant recipients where it is the most prevalent tumor type in a population at higher risk for malignancy in general, and where anti-PD-1 therapy provides a significant risk of rejection of the transplanted organ. The U.S. Food and Drug Administration (FDA) has accepted the protocol for this clinical trial under the Company’s previously accepted Investigational New Drug Application for RP1. The clinical trial is intended to enroll approximately 30 patients and assess the safety and efficacy of RP1 in liver and kidney transplant recipients with recurrent CSCC. Replimune expects to initiate the clinical trial in the first quarter of 2020.

RP1 – Additional clinical trial intended of RP1 in combination with an anti-PD-1 therapy in anti-PD-1 refractory melanoma patients. Based on the clinical efficacy data to date with RP1 in melanoma, the Company has decided to conduct a new clinical trial of RP1 in combination with an anti-PD-1 therapy in anti-PD-1 refectory melanoma patients. Discussions are underway to determine the particular anti-PD-1 therapy to be used. The trial is expected to begin enrollment in 2020.

RP2 – Initiation of the Phase 1 clinical trial of RP2 alone and in combination with Opdivo. RP2 is based on RP1 but additionally expresses a genetically encoded anti-CTLA-4 antibody-like molecule. The addition of anti-CTLA-4 is intended to block the inhibition of the initiation of immune responses otherwise caused by CTLA-4. The clinical trial is designed to assess the safety, tolerability and to determine the optimal dose of RP2 alone and in combination with Opdivo and is being conducted under a clinical trial collaboration and agreement with BMS for the supply of Opdivo.

RP3 – The Phase 1 clinical trial of RP3 alone and in combination with an anti-PD1 therapy remains on track to initiate in 2020. RP3 is a further armed oncolytic immuno-gene therapy which expresses two immune co-stimulatory activating ligands (CD40L and 4-1BBL) in addition to the GALV-GP R- fusogenic protein and anti-CTLA-4.

Build-out of Replimune’s manufacturing facility to support late-stage development and commercialization remains on schedule. The 63,000-square-foot facility in Framingham, MA is intended to provide multi-product manufacturing capabilities for Replimune’s Immulytic product candidates. The capacity of this facility will be sufficient to support full commercialization of the Company’s product candidates. An occupancy certificate for the facility has been obtained and technology transfer is underway.
Financial Highlights

Replimune reported a net loss of $11.1 million for the quarter ended September 30, 2019 compared with $6.5 million for the same period in the prior year.

Research and development expenses for the quarter ended September 30, 2019 were $8.2 million compared with $5.0 million for the same period in the prior year. The increase in research and development expenses was primarily driven by additional costs related to Replimune’s preclinical and clinical development activities for its pipeline.

General and administrative expenses for the quarter ended September 30, 2019 were $4.1 million compared with $2.1 million for the same period in the prior year. The increase in general and administrative expenses was primarily due to an increase in employee headcount, professional fees and facility costs.

Replimune ended the quarter with $109.9 million in cash, cash equivalents, and short-term investments, compared with $134.8 million as of March 31, 2019.

Based on its current operating plan, Replimune expects that its current cash, cash equivalents, and short-term investments will enable it to fund its operating expenses and capital expenditure requirements into the second half of calendar year 2021.

On November 11, 2019 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer, and other indications, reported its financial results for the third quarter of 2019 ended September 30, 2019, and provided an update on the Company’s recent and future developments (Press release, Pieris Pharmaceuticals, NOV 11, 2019, View Source [SID1234550862]).

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"The recent presentations of clinical data for our two lead programs, PRS-060 and PRS-343, represent critical inflection points in the history of Pieris," said Stephen S. Yoder, President and Chief Executive Officer of Pieris. "In October, we presented positive data from our ongoing phase 1b study of PRS-060, an inhaled IL-4 receptor alpha antagonist for moderate-to-severe asthma, and we continue to be excited about the program as we plan with AstraZeneca to move into phase 2 next year. Over the weekend, we presented promising data from our phase 1 dose-escalation study of PRS-343, a 4-1BB/HER2 bispecific for HER2-positive solid tumors, demonstrating single-agent activity that we believe is linked to 4-1BB engagement, and we look forward to initiating an indication-specific expansion study for this drug candidate next year. Our recently-announced financing, supported not only by key existing shareholders but also by fundamental focused new investors, will enable more near-term data-driven clinical development investment and is intended to provide a funding mechanism to facilitate Pieris’ ability to opt-into co-development of PRS-060 with AstraZeneca if phase 2a data are positive."

PRS-060: Pieris presented data from the phase 1b placebo-controlled multiple ascending dose study of PRS-060/AZD1402, an inhaled IL-4 receptor alpha antagonist for moderate-to-severe asthma, at the 2019 European Respiratory Society International Congress on October 1st. In that analysis, PRS-060/AZD1402 was found to be safe and well tolerated at all doses, led to a statistically significant reduction in fractional exhaled nitric oxide (FeNO) relative to placebo, and showed dose-dependent systemic target engagement in patients with mild asthma and elevated levels of FeNO (≥ 35 ppb). Following the presentation of these encouraging data, AstraZeneca and Pieris have been preparing to move into a phase 2a study in moderate-to-severe asthmatics next year. Upon completion of that study, which will be sponsored and funded by AstraZeneca, Pieris will have options to co-develop and co-commercialize the drug candidate in the United States.
PRS-343: Pieris presented data from its phase 1 dose-escalation monotherapy study of PRS-343, a 4-1BB/HER2 bispecific for HER2-positive solid tumors, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting on November 9th. PRS-343 was safe and well tolerated at all doses and schedules tested, demonstrated anti-tumor activity in a heavily pre-treated patient population across multiple tumor types, and showed a potent increase in CD8+ T cell numbers in the tumor microenvironment of responders, indicative of 4-1BB agonism on T cells. Pieris continues to enroll patients in that study at higher dose cohorts and plans to initiate an indication-specific expansion trial next year. The Company also continues to enroll the dose-escalation phase 1 study of PRS-343 in combination with atezolizumab, with the objective of interrogating the synergy between 4-1BB agonism and PD(L)-1 blockade, and will report emerging data from that study at the Pieris R&D day on November 19th.
Immuno-oncology Pipeline: Pieris plans to file an IND application for PRS-344, a 4-1BB/PD-L1 bispecific that the Company is developing as part of its collaboration with Servier, in the first half of next year. Pieris holds exclusive commercialization rights for PRS-344 in the United States and will receive royalties on ex-U.S. sales for this program.
R&D Day: Pieris will host an R&D day in New York on Tuesday, November 19th from 12:00-3:30 PM EST. The event will be accessible via a live webcast through this link beginning at 12:30 PM EST.
Private Placement: The Company completed a $32 million private placement led by BVF Partners L.P., with significant additional participation from EcoR1 Capital, Aquilo Capital Management, Surveyor Capital (a Citadel company), and Samsara BioCapital. The placement consisted of 9,014,960 units at a price of $3.55 per unit, with each unit consisting of (i) one share of common stock or 0.001 non-voting Series C convertible preferred stock and (ii) one warrant to purchase one share of common stock at an exercise price of $7.10 per share. Each share of non-voting Series C convertible preferred stock is convertible into 1,000 shares of Pieris common stock, provided that conversion will be prohibited if, as a result, the holder and its affiliates would own more than 9.99% of the total number of shares of Pieris common stock then outstanding. The warrants are intended to facilitate Pieris’ exercise of its co-development option for PRS-060/AZ1402 following the conclusion of a positive phase 2a study. If top-line results of that study disclose achievement of the primary efficacy endpoint and the stock reaches a pre-specified price, then the warrants will expire 60 days following such disclosure and may only be exercised for cash. Otherwise, the warrants will be exercisable for a period of five years from the date of issuance.
Third Quarter Financial Update:

Cash Position – Cash, cash equivalents, and investments totaled $86.2 million as of September 30, 2019, compared to cash equivalents, and investments totaling $128.1 million as of December 31, 2018. This amount excludes the $32 million in gross proceeds from the November 2019 financing. Included in the Company’s cash spend during the third quarter of 2019 was a one-time $2.3 million payment to the Technical University of Munich for sub-license royalties due on upfront and milestone payments related to collaboration agreements signed in 2017 and 2018.

R&D Expense – R&D expenses were $13.2 million for the quarter ended September 30, 2019, compared to $11.4 million for the quarter ended September 30, 2018. The Company’s increase in R&D expenses reflects higher (albeit reimbursable) manufacturing efforts related to PRS-060/AZD1402 as part of phase 2a readiness activities for the program, as well as higher personnel and allocated facility costs due to growth in the Company’s R&D organization to support higher levels of pre-clinical and clinical activities.

G&A Expense – G&A expenses were $4.8 million for the quarter ended September 30, 2019, compared to $4.7 million for the quarter ended September 30, 2018. There was no significant change in the composition of G&A expenses on a quarter over quarter basis.

Net Loss – Net loss was $2.6 million or $(0.05) per share for the quarter ended September 30, 2019, compared to a net loss of $6.6 million or $(0.11) per share for the quarter ended September 30, 2018.

Conference Call:

Pieris management will host a conference call beginning at 8:00 AM EST on Monday, November 11, 2019 to provide a corporate update. Individuals can join the call by dialing +1-877-407-8920 (US & Canada) or +1-412-902-1010 (International). An archived replay of the call will be available by dialing +1-877-660-6853 (US & Canada) or +1-201-612-7415 (International) and providing the Conference ID #: 13661472.

On November 11, 2019 Heat Biologics, Inc. (NASDAQ:HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, reported that the Company presented additional positive Phase 2 interim top line data from Cohort B of the Company’s Phase 2 trial of its T-cell activating cell-based therapy, HS-110, in combination with Opdivo (nivolumab) in advanced non-small cell lung cancer (NSCLC) (Press release, Heat Biologics, NOV 11, 2019, View Source [SID1234550861]). The data was presented at a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting on November 8th.

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Cohort B enrolled patients who had previously received a minimum of 4 months of checkpoint inhibitor (CPI) therapy and whose disease had subsequently progressed, a patient population with a significant unmet medical need. 61% of patients achieved disease stabilization per iRECIST. Median progression-free survival was 3.2 months and median overall survival was 11.8 months. Moreover, patients experiencing dermal injection site reactions (ISR) had statistically significant improvement in PFS and OS compared to those without ISR (Hazard Ratio = 0.40, p=0.0068 and Hazard Ratio = 0.16, p=0.0005, respectively).

George Peoples, M.D., FACS, Heat Biologics’ Chief Medical Advisor, commented, "This data is extremely promising, as the combination of HS-110 and nivolumab may provide patients with treatment options other than salvage cytotoxic chemotherapy. Consistent with our previously reported data, the benefit of HS-110 in combination with nivolumab is independent of PD-L1 expression and we are seeing positive data in low PD-L1 patients (<1%) that typically do not respond well to checkpoint inhibitor monotherapy."

Dr. Peoples continued, "This data suggests re-challenging the immune system with nivolumab and HS-110 after checkpoint inhibitor treatment failure may restore responsiveness and clinical benefit. Further supporting the mechanism of action of HS-110, patients experiencing dermal injection site reactions (ISR) had statistically significant improvement in PFS and OS compared to those without ISR."

This combination of HS-110 and nivolumab is well-tolerated and when compared to CPI monotherapy, no increase in the incidence of immune-related adverse events has been observed.

Jeff Wolf, Heat Biologics’ CEO, commented, "This data is very encouraging as the combination of HS-110 with nivolumab may address an important unmet need among patients whose disease has progressed following checkpoint inhibitor therapy. These patients currently have limited treatment options. We look forward to advancing our clinical trials and exploring potential partnership and other strategic options to move this program forward."