On May 15, 2019 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is generating red blood cells and bioengineering them into an entirely new class of cellular medicine reported first quarter 2019 financial results and provided an overview of operational progress (Press release, Rubius Therapeutics, MAY 15, 2019, View Source [SID1234536305]). In addition, Rubius announced that company president, Torben Straight Nissen, Ph.D., will be leaving the Company at the end of July 2019, to join Flagship Pioneering where he has held a venture partner role since joining Rubius in 2016.

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"Rubius has made significant progress this year, including the clearance of our first Investigational New Drug application for RTX-134 for the treatment of patients with phenylketonuria," said Pablo J. Cagnoni, M.D., chief executive officer of Rubius Therapeutics. "We plan to begin enrolling patients in the Phase 1b trial during the second quarter with initial clinical data expected during the second half of the year. We presented important preclinical data from our emerging oncology portfolio at AACR (Free AACR Whitepaper), demonstrating promising anti-tumor activity with no observed toxicities for our lead product candidates, RTX-240 and RTX-224, for the treatment of solid tumors and RTX-aAPC for the treatment of HPV-positive tumors. The year is off to a great start as we continue to advance our Red Cell Therapeutics towards our ultimate goal of treating patients who are underserved by available therapies."

"We are grateful to Torben for all his contributions towards building a world-class organization and for remaining with Rubius since I joined the company to continue supporting the scale-up of our manufacturing capabilities," continued Dr. Cagnoni. "During his tenure, Torben also took part in executing key financings, made important leadership hires and helped drive the formation and advancement of our portfolio of programs that target rare diseases, cancer and autoimmune diseases. We wish him the best going forward."

"I am very proud of the hard work, dedication and innovative spirit of the Rubius team that has led the company to where it is today," said Dr. Straight Nissen. "I believe Rubius’ Red Cell Therapeutics approach has the potential to transform the future of cellular medicine, and I look forward to following the company as they work towards bringing these important therapies to patients. I wish all my talented colleagues at Rubius continued success as I transition to focus on earlier stage platform companies within the Flagship Pioneering ecosystem."

Dr. Straight Nissen will continue to provide consulting services to Rubius into 2020. With his departure, Spencer Fisk, senior vice president of technical operations, and Thomas Wickham, Ph.D., senior vice president of discovery, will report directly to Dr. Cagnoni.

First Quarter Program Highlights and Updates

In March 2019, Rubius received clearance from the U.S. Food and Drug Administration (FDA) of the Company’s Investigational New Drug (IND) application for RTX-134. RTX-134 is an allogeneic, off-the-shelf cellular therapy for the potential treatment of patients with phenylketonuria (PKU), a rare, inherited metabolic disorder that is characterized by the body’s inability to metabolize the essential dietary amino acid, phenylalanine.

oThe Company expects to enroll up to 10 adult patients with PKU in the Phase 1b trial, with enrollment expected to begin during the second quarter of 2019 and initial clinical data anticipated in the second half of 2019, including:

Preliminary safety;

Longevity of RTX-134 cells in circulation;

Proof-of-mechanism as measured by production of trans-cinammic acid, the metabolite of phenylalanine when degraded by phenylalanine ammonia lyase (PAL); and

Selection of a preliminary dose and schedule.

On April 2, 2019, Rubius presented preclinical data from its emerging oncology pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

oRTX-240 (4-1BBL and 1L-15TP) and RTX-224 (4-1BBL and IL-12) are allogeneic cellular therapy product candidates that are engineered to replicate the human immune system by stimulating the adaptive and innate immune systems to induce an immune response.

RTX-240 and RTX-224 each demonstrated potent activation of the immune system, anti-tumor activity and a potentially broad therapeutic window when compared to agonists antibodies or recombinant cytokines.

Additionally, RTX-224 in combination with an anti-PD-1 antibody demonstrated substantial tumor shrinkage in a difficult-to-treat MC38 colon cancer model.

oRed Cell Therapeutic (RCT) artificial antigen presenting cells, or RTX-aAPCs, are engineered to induce a tumor-specific response by expanding tumor-specific T cells against a target antigen.

RTX-aAPCs activated and significantly expanded antigen-specific T cells to promote substantial tumor regressions, leading to increased survival with no observed toxicity, in an OVA-positive murine model.

The Company continued to strengthen its leadership by appointing Natalie Holles to its board of directors and Greg Whitehead as senior vice president and chief quality officer, while bolstering internal capabilities in discovery, platform development and technical operations.

Rubius remains on track to submit a total of four to five INDs across 2019 and 2020, while continuing to progress additional pipeline programs in rare diseases, cancer and autoimmune diseases.

First Quarter Financial Results

Net loss for the first quarter of 2019 was $32.6 million or $0.42 per common share, compared to $14.4 million or $1.72 per common share in the first quarter of 2018.

In the first quarter of 2019, Rubius invested $20.9 million in research and development (R&D) related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, compared to $9.5 million in the first quarter of 2018. The year-over-year increase was due to an additional $3.6 million of costs incurred in preparation for the Phase 1b clinical trial for RTX-134, and $9.3 million was associated with personnel costs, stock-based compensation, facility and laboratory costs driven by increases in R&D headcount and expanded research activities to support Rubius’ goal of delivering four to five IND’s across 2019 and 2020. These increases were offset by a decrease in external manufacturing and research costs that were not related to programs.

G&A expenses were $13.5 million during the first quarter of 2019, as compared to $5.1 million for the first quarter of 2018. The higher costs were primarily driven by a $7.4 million increase in personnel costs, stock-based compensation and facility costs, due to increased headcount in our general and administrative function, as well as increases in professional fees and infrastructure costs to support the Company’s growth and to operate as a public company.

Cash Position

As of March 31, 2019, cash, cash equivalents and investments were $378.9 million as compared to $404.1 million as of December 31, 2018, providing Rubius with a cash runway into 2021. During the quarter, the Company used $22.9 million of cash to fund operations and $4.2 million to fund capital expenditures.

On May 15, 2019 Heat Biologics, Inc. (Nasdaq: HTBX), a biopharmaceutical company developing therapies designed to activate a patient’s immune system against cancer, reported financial and clinical updates for the first quarter ended March 31, 2019 (Press release, Heat Biologics, MAY 15, 2019, View Source [SID1234536304]).

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Jeff Wolf, Heat’s CEO, commented, "We are making progress with our Phase 2 clinical trial investigating HS-110 for advanced non-small cell lung cancer (NSCLC) in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, Opdivo (nivolumab) and Merck’s KEYTRUDA (pembrolizumab). Most notably, we announced positive interim Phase 2 data at the ASCO (Free ASCO Whitepaper)/SITC Clinical Immuno-Oncology Symposium where we observed a survival benefit in patients with low CD8+ "cold" tumors compared to high CD8+ patients. The Cohort B data was especially encouraging, as the addition of HS-110 to nivolumab may restore anti-tumor activity in patients whose disease has progressed after checkpoint inhibitor therapy."

"We anticipate filing two INDs early this summer: HS-130, the first dual-acting immunotherapy designed to deliver local T-cell activation and co-stimulation, as well as PTX-35, our first-in-class T cell costimulator antibody. We recently presented a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, in which we reported efficacy in a mouse model, demonstrating that the combination of HS-110 with OX40L co-stimulation has the potential to dramatically enhance anti-tumor immune responses via the activation and expansion of CD8+, tumor antigen-specific, T effector cells. We also remain encouraged by the preliminary pre-clinical efficacy and safety data of PTX-35, which show activity with a favorable safety profile across a wide range of doses."

"We ended the quarter with approximately $23.5 million of cash, cash equivalents and short-term investments. We expect to receive an additional $6.9 million in grant funds from Cancer Prevention Research Institute of Texas (CPRIT) after filing our IND for PTX-35."

First Quarter 2019 Financial Results

Recognized $0.7 million of grant revenue for qualified expenditures under the CPRIT grant.

Research and development expenses increased to $3.2 million for the quarter ended March 31, 2019 compared to $2.9 million for the quarter ended March 31, 2018. The $0.3 million increase is due to the increased enrollment in the Phase 2 portion of our multi-arm NSCLC clinical trial, stock-based compensation, and the PTX expense as we continue pre-clinical development of the PTX-35 program.

General and administrative expenses were approximately $3.3 million for the quarter ended March 31, 2019 compared to $1.8 million for the quarter ended March 31, 2018. The $1.6 million increase is primarily attributable to increased stock-based compensation expense.

Net loss attributable to Heat Biologics was approximately $5.7 million, or ($0.17) per basic and diluted share for the quarter ended March 31, 2019 compared to a net loss of approximately $3.3 million, or ($0.71) per basic and diluted share for the quarter ended March 31, 2018.

As of March 31, 2019, the Company had approximately $23.5 million in cash, cash equivalents and short-term investments.

On May 15, 2019 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that the U.S. Food and Drug Administration (FDA or Agency) has lifted the partial clinical hold on AIM2CERV, the company’s Phase 3 clinical trial of axalimogene filolisbac (AXAL) for the treatment of patients with high-risk locally advanced cervical cancer (Press release, Advaxis, MAY 15, 2019, View Source [SID1234536303]). In its letter, the FDA acknowledged that the company satisfactorily addressed all hold questions.

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As announced on January 23, 2019, the FDA placed a partial clinical hold on this study relating to the Agency’s requests for additional information pertaining to certain AXAL chemistry, manufacturing and controls (CMC) matters. The Agency did not cite any safety issues related to the trial and all enrolled patients continued to receive treatment, per the trial protocol. However, no new patients were permitted to enroll in AIM2CERV during this partial hold.

"The Advaxis team worked diligently to provide a comprehensive response back to the FDA’s requests for additional CMC information, and through constructive dialogue, we successfully resolved the partial clinical hold," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "Our AXAL product has demonstrated a manageable safety profile in the over 400 patients we have dosed to date, and we look forward to working with our clinical research organization to reopen enrollment at AIM2CERV sites. We remain focused on our mission of developing innovative therapies to address unmet needs and improving the lives of people with cancer."

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a Phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38% in 50 patients. This is a 52% improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.

Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications.

On May 15, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, and Alpine Immune Sciences, Inc., Seattle, WA, (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for autoimmune diseases and cancer, reported a collaboration and license agreement to develop next-generation SPEAR T-cell products which incorporate Alpine’s secreted and transmembrane immunomodulatory protein (termed SIP and TIP) technology (Press release, Adaptimmune, MAY 15, 2019, View Source;p=RssLanding&cat=news&id=2398682 [SID1234536302]). This collaboration will further enhance Adaptimmune’s efforts to design and develop next-generation SPEAR T-cell therapies.

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"Our directed evolution platform has successfully generated many unique, multi-functional protein domains designed to favorably modulate the tumor microenvironment via validated immune targets," said Stanford Peng, MD PhD, Alpine’s President and Head of Research & Development. "We look forward to working with Adaptimmune to develop next-generation SPEAR T-cell therapies to achieve improved clinical outcomes."

Alpine and Adaptimmune will collaborate on a specified number of programs to develop SIP and TIP candidates with tailored affinities and modulatory activities that may enhance the anti-tumor responses seen with Adaptimmune’s SPEAR T-cells.

Alpine and Adaptimmune will collaborate on a specified number of programs to develop SIP and TIP candidates with tailored affinities and modulatory activities that may enhance the anti-tumor responses seen with Adaptimmune’s SPEAR T-cells.

Under the terms of the collaboration agreement, Adaptimmune will provide an upfront payment and research funding for ongoing programs. In addition, Alpine may be eligible for downstream development and commercialization milestones up to $288M, if all pre-specified milestones for each program are achieved.

Alpine will receive low-single digit royalties on worldwide net sales of the applicable products.

On May 14, 2019 Sosei Group Corporation ("the Company"); (TSE: 4565) reported encouraging progress and initial success of its strategic multi-target drug discovery collaboration with Pfizer (Press release, Sosei Heptares, MAY 14, 2019, https://www.prnewswire.com/news-releases/sosei-heptares-reports-progress-with-pfizer-as-multi-target-collaboration-delivers-first-candidate-for-clinical-advancement-300849503.html [SID1234552772]). The research phase of the collaboration has delivered several milestones leading to the advancement of new potential candidate programs against G protein-coupled receptor (GPCR) targets nominated by Pfizer in major disease areas.

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These targets have clinical and biological validation as key points for therapeutic intervention targeting metabolic and inflammatory diseases but have proved challenging to address with conventional discovery approaches because of inherent technical challenges. To address these challenges, Sosei Heptares and Pfizer scientists have worked closely together to leverage their complementary expertise in enabling GPCR-focused structure-based drug design (SBDD) and development initially directed towards up to ten GPCR targets nominated by Pfizer.

In addressing these targets, Sosei Heptares has delivered stabilized receptors (StaR proteins), X-ray structures and biophysical data on certain programs, triggering milestone payments from Pfizer, including US$3 million announced today. Further milestones payments are contemplated under the agreement, with potential for royalties also payable provided the criteria under the agreement are satisfied. Pfizer also made a US$33 million equity investment in Sosei Heptares in 2015. In the future, Pfizer and Sosei Heptares anticipate publication of select research findings from their collaboration.

Dr. Malcolm Weir, Executive VP and Chief R&D Officer of Sosei Heptares, said: "Pfizer has a real appreciation of the potential value that structural studies can bring to drug design and discovery. Sosei Heptares is delighted with the relationship and interaction that has developed between our respective scientists since starting the collaboration and particularly with the achievement announced today. This was made possible, in part, through the collaborative application of our SBDD platform, which is also being used in other promising programs. We look forward in the coming years to the continued progress of these programs."

Charlotte Allerton, Head of Medicine Design at Pfizer said: "We are very pleased with the progress achieved through our collaboration with Sosei Heptares and are optimistic about our future work together. Sosei Heptares’ GPCR-focused structure-based drug design provides us with a valuable new approach to potentially enable the design of small molecules to modulate important disease targets."

Additional information about the collaboration with Pfizer

Sosei Heptares and Pfizer entered into a strategic drug discovery collaboration in November 2015 to research and develop potential new medicines directed at up to ten G protein-coupled receptor (GPCR) targets across multiple therapeutic areas.

Sosei Heptares will use its proprietary GPCR structure-guided platform to help deliver stabilised GPCRs (StaR proteins), high-resolution crystal structures and other technologies to support the discovery of potential novel agents directed to the GPCR targets selected by Pfizer. Pfizer will be responsible for developing and commercialising any potential therapeutic agents (small molecules or biologics) for each target and will have exclusive global rights to any potential resulting agents.

Sosei Heptares is eligible to receive research, development, regulatory and commercial milestone payments and tiered royalties on the net sales of any products that are commercialized by Pfizer. In addition, Pfizer made an equity investment in Sosei Heptares upon signing.