On April 1, 2020 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and the innovative biotechnology company panCELLa Inc. reported that the companies have entered into a licensing and investment agreement (Press release, Evotec, APR 1, 2020, View Source;announcements/press-releases/p/evotec-expands-its-ipsc-based-cell-therapy-platform-evocells-through-licensing-agreement-with-pancella-5921 [SID1234556085]).

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Under the terms of the agreement, Evotec will receive a non-exclusive licence to access panCELLa’s proprietary iPS cell lines "iACT Stealth Cells", which are genetically modified to prevent immune rejection of derived cell therapy products ("cloaking"). Furthermore, Evotec will also have access to a new-generation cloaking technology known as hypoimmunogenic cells. In addition, the "FailSafe" mechanism effectively addresses a key challenge in iPSC-based cell therapy, potential tumour formation by residual undifferentiated cells.

Using the cell lines, Evotec will be able to develop iPSC-based, off-the-shelf cell therapies with long-lasting efficacy that can be safely administered to a broad population of patients without the use of medication to supress the patients’ immune system. With a growing portfolio of iPSC-based cell therapy projects at Evotec, access to research as well as GMP-grade iPSC lines modified with one or both of the panCELLa technologies significantly accelerates Evotec’s cell therapy discovery and development efforts. Modified iPSC lines will be available for the development of cell therapy approaches across a broad range of indications by Evotec and potential partners. Furthermore, Evotec has made an investment to take a minority stake in panCELLa and has nominated Dr Andreas Scheel to join panCELLa’s supervisory board.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "Cell therapies hold enormous potential as truly regenerative or curative approaches for a broad range of different diseases with significant medical need. Integrating panCELLa’s technology and cell lines into our ongoing proprietary research and development efforts strengthens Evotec’s position in cell therapy. It is our goal to provide safe highly-effective cell therapy products to as many patients as possible. In addition to small molecules and biologics, cell therapy will become yet another major pillar of Evotec’s multimodality discovery and development platform."

Mahendra Rao, MD, PhD, CEO at panCELLa, added: "We welcome the partnership with Evotec. Evotec’s widely recognised expertise and existing portfolio of iPSC-related technology platforms will allow panCELLa to rapidly advance its own therapeutic interests in NK cell therapy, pancreatic islet production and iPSC-derived MSC platform, in addition to enabling panCELLa to make its platform technologies widely available. I believe that the investment by Evotec in our company is a strong validation of the leading role of panCELLa in the field of regenerative medicine and in the utility of its platform technologies. We welcome Dr Andreas Scheel to our Board."

On April 1, 2020 Stamford pharmaceuticals a clinical stage immunology and inflammation focused company developing novel combination therapies for cancers, reported a clinical collaboration with Roche (SIX:RO, ROG) to explore SP-002 (formerly ASN-002/TG1042), Stamford’s adenoviral vector immunotherapy, in combination with Roche’s vismodegib (Erivedge), a Hedgehog Pathway inhibitor approved for the treatment of adult patients presenting with locally advanced and metastatic basal cell carcinoma (Press release, Ascend Biopharmaceuticals, APR 1, 2020, View Source [SID1234556083]). The combination study will be conducted in patients with multiple basal cell carcinomas (BCCs).

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"This collaboration is an opportunity to create a new treatment paradigm for patients with multiple BCCs." said Clement Leong, PhD., Stamford Pharmaceutical’s Chief Executive Officer. "We believe that SP-002 when combined with vismodegib has potential to enhance the response rate1 of BCC lesions directly injected with SP-002 but can also confer responses in distant non-injected BCCs. This would represent a major advancement for the management of patients with multiple BCCs who currently have to endure the morbidity that arises from many surgical procedures."

SP-002 is an adenoviral-5 vector-based immunotherapy encoding the gene for human Interferon-. It will be evaluated in combination with a reduced duration of vismodegib treatment. It is expected that the combination will alter the tumor microenvironment to support more potent and durable anti-tumor responses, while using a shorter duration of vismodegib treatment to optimize tolerability. Stamford 1

Based on a composite endpoint of Complete Response (clinical assessment) and Histological Clearance W: www.stamfordpharmaceuticals.com E: info@ stamfordpharmaceuticals.com US Connecticut Office Melbourne Office Level 2, 330 Railroad Ave, 1/159 Dorcas Street Greenwich, CT 0683 South Melbourne, VIC 3205 USA Australia Pharmaceuticals plans to initiate an open-label, multicenter Phase 2a clinical trial of SP-002 administered as an intra-lesional injection to patients who have multiple basal cell carcinomas in both the basal cell nevus and sporadic BCC populations. The primary objective of the study is to evaluate the efficacy, safety and tolerability of SP-002 in combination with vismodegib in both target (lesions injected with SP-002) and non-target (non-injected) lesions. Stamford Pharmaceuticals will be the sponsor of the study and Roche will provide vismodegib and clinical and scientific support for the study.

On April 1, 2020 GenScript, a world leading biotechnology company, reported the commercial launch of its neoantigen peptide synthesis service for biotech and pharma companies developing personalized cancer therapeutics (Press release, GenScript, APR 1, 2020, View Source [SID1234556082]). The service builds on GenScript’s work over the past year producing 2,500 highly difficult neoantigen peptides for more than 50 of the world’s leading immuno-oncology companies.

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Unlike traditional targets such as tumor-associated antigens, neoantigens are novel peptides only present within tumor cells and not in healthy tissue. Because of this, neoantigen-based immunotherapy stimulates stronger anti-tumor immune responses with fewer negative and off target effects than other immunotherapies. When generating personalized cancer vaccines or T-cell therapies, neoantigen peptides are critical for in-vitro functionality screening, pre-clinical safety analysis, and post-clinical efficacy screening; however, manufacturing these peptides is very challenging due to extreme hydrophobicity and other physiochemical properties.

GenScript partnered with several T-cell therapy and personalized cancer vaccine companies to develop the infrastructure to reliably manufacture difficult peptides for its neoantigen peptide synthesis platform. This effort resulted in several successful projects, most recently Avidea Technologies’ SNAP vaccine platform, as reported in Nature Biotechnology, as well as a collaboration involving 3T Biosciences’ proprietary T-cell therapy screening platform.

"3T Biosciences has been working with GenScript since 2017 to generate thousands of peptides to understand how T-cell receptors recognize their targets. With that information we can better understand how to identify novel targets in solid tumors and generate safe and effective T-cell receptors," said Marvin Gee, Ph.D., 3T Biosciences’ co-Founder and Head of Target Discovery. "The 3T technology is multi-faceted due to the ability to uncover specificities in any T-cell- mediated disease, covering not only oncology but also allergy, inflammation, autoimmune disease, and infection, which is pertinent for the ongoing situation with COVID-19."

GenScript has been synthesizing peptides for more than 15 years, successfully delivering over 600,000 high-quality peptides – a 98 percent delivery rate – to more than 10,000 scientists worldwide. The company has developed multiple innovative synthesis technologies, including its patented NeoPreTM neoantigen synthesis prediction algorithm. The algorithm is applied during neoantigen peptide synthesis to analyze a peptide’s physiochemical properties (hydrophobicity, charge, aggregation potential, etc.) in order to determine which of GenScript’s technologies provides the highest chance of successful synthesis. From there, highly skilled GenScript scientists synthesize each peptide through the recommended methodology, ranging from automated microwave technology for fast turn-around time to manual liquid phase technology for difficult to purify peptides with high yields.

"GenScript is committed to developing innovative new synthesis platforms and bioinformatics tools to help our customers bring safe and effective life-saving treatments to patients more quickly and efficiently," said Xin Zhang, GenScript Biotech’s associate director of peptide services. "Neoantigen peptide synthesis is significantly challenging, but by leveraging our microwave, solid, and liquid phase synthesis platforms along with our new NeoPreTM production algorithm, we are able to consistently produce difficult peptides for cancer research and drug development."

Peptide production is guided by the diverse needs of each project, including number of peptides, yields, turnaround time, specialized quality control requirements, and pooling. GenScript’s flexible approach allows for customization in ways that traditional GMP providers find difficult. For example, groups developing personalized cancer vaccines will often initially require large libraries of micro-scale peptides for functional validation of neoantigen candidates. Once identified, these neoantigen peptides will then need to be produced at large yields with extremely high purity in order to generate vaccine prototypes for animal studies.

GenScript’s service also includes stage-specific tools and a library design program, which assists customers in creating their own peptide libraries. Currently, GenScript offers seven different types of libraries, including alanine scanning, overlapping, and T-cell truncation to help customers optimize the safety and efficacy of their neoantigen therapeutics.

On April 1, 2020 Stealth BioTherapeutics Corp (NASDAQ: MITO), a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction, reported financial results for the year ended December 31, 2019 and announced recent business highlights (Press release, Stealth Biologics, APR 1, 2020, View Source [SID1234556081]).

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"We are off to a strong start in 2020, having honed our focus on Barth and our planned expansion into other rare metabolic cardiomyopathies, while continuing to execute on the significant promise of our ophthalmic and other pipeline programs. By decisively reducing expenses in January, our cash and cash equivalents are sufficient through key Barth regulatory interactions in the second half of 2020, bringing us closer to a potential approval with an opportunity for a rare pediatric voucher and expedited regulatory review," said Reenie McCarthy, Chief Executive Officer at Stealth. "We hope to complete enrollment of our Phase 2b study in dry AMD during the second half of this year, keeping us on-track for a second half of 2021 top-line read-out. We are actively planning development initiatives in other rare metabolic cardiomyopathies, on which we hope to engage with the FDA this year. We are also rapidly advancing our pipeline of novel mitochondrial medicines, with SBT-272 being assessed in a Phase 1 clinical trial, preclinical data read-outs expected this year for SBT-272 in amyotrophic lateral sclerosis and multiple system atrophy and SBT-259 in Charcot-Marie-Tooth, and lead optimization underway for our SBT-550 series, targeting the ferroptosis pathway of cell death implicated in neurodegenerative diseases such as Parkinson’s."

Fourth Quarter 2019 and Recent Highlights

Announced Barth rare pediatric designation. In March 2020, the Company announced receipt of Rare Pediatric Disease (RPD) designation from the U.S. Food and Drug Administration (FDA) for elamipretide for the treatment of Barth syndrome. Under this program, upon FDA priority review and approval of elamipretide for Barth syndrome, the Company would be eligible for a voucher that can be used to obtain priority review for a subsequent drug application.
Announced positive Barth data from natural history efficacy study. In February 2020, the Company announced positive results from its SPIBA-001 natural history comparative control efficacy study in Barth patients, demonstrating a greater than 80 meter improvement in the primary endpoint of 6 Minute Walk Test at one year compared to natural history controls (p=0.0005).
Expanded clinical pipeline. In January 2020, the Company initiated a first-in-human Phase 1 clinical trial evaluating its second-generation pipeline compound, SBT-272, in healthy subjects. The Company anticipates that preclinical data expected later this year in models of amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) will help inform SBT-272’s clinical development pathway for rare neurodegenerative diseases.
Implemented strategic repositioning. In January 2020, the Company implemented strategic actions to reduce costs and reposition its focus on Barth and other rare metabolic cardiomyopathies, in addition to its ophthalmic and pipeline neurology programs following 2019 year-end announcement of the Company’s MMPOWER-3 clinical study results.
Announced improvement in cardiac function in Barth. In October 2019, data presented at the American Society of Human Genetics (ASHG) 2019 Annual Meeting showed that treatment with elamipretide was associated with a significant increase in average cardiac stroke volume, or the amount of blood pumped by the heart’s left ventricle per contraction, in Barth subjects, measured from the trial baseline (40.8 mL) to week 36 (51.8 mL) of the open-label extension (p<0.01).
Alexion collaboration. In October 2019, the Company announced an option agreement with Alexion, in connection with which it received gross proceeds of $30 million. Although Alexion has declined to exercise this option, the gross proceeds provided the Company with flexibility to consider its strategic financing options and develop a Barth regulatory path.
Key Upcoming Milestones

Anticipated guidance from FDA meeting on Barth expected midyear 2020.
Complete enrollment of Phase 2b clinical trial in dry AMD expected second half of 2020.
Pre-clinical data for SBT-272 in ALS and MSA and for SBT-259 in CMT expected by year-end.
2019 Financial Results

Revenue: In 2019, the Company recognized $21.1 million in revenue associated with the Alexion arrangement. The revenue represents the portion of the non-refundable upfront payments that were recognized in full upon the delivery of the topline data for the Company’s MMPOWER-3 trial. Alexion terminated the arrangement and as such, no additional revenue will be recognized.

Research and Development (R&D) Expenses: R&D expenses decreased by $8.5 million to $44.6 million for the year ended December 31, 2019, from $53.1 million for the year ended December 31, 2018. This decrease was primarily from a net decrease of $8.5 million in clinical trial costs due to the timing of trials that ended in 2018, a $2.8 million decrease in contract manufacturing, and a $0.9 million decrease in discovery related expenses due to timing of activities. These decreases were offset in part by increases of $3.6 million in employee and consultant related expenses driven by continued build-out of clinical, medical affairs and regulatory functions and $0.1 million in other costs.

General and Administrative (G&A) Expenses: G&A expenses increased by $0.1 million to $22.3 million for the year ended December 31, 2019, from $22.2 million for the year ended December 31, 2018. The increase was primarily attributable to a net $2.3 million increase in pre-commercial activities including building market disease awareness, a $1.8 million increase in professional services for activities attributable to operating as a public company, an increase of $3.2 million in employee related costs offset by a decrease of $6.7 million in costs associated with 2018 financing efforts and a decrease in IP legal fees of $0.5 million.

Other Expenses: Other expenses increased by $4.5 million to $25.9 million for the year ended December 31, 2019 from $21.4 million for the year ended December 31, 2018. The increase in other expenses is primarily attributable to a $22.7 million loss on extinguishment of debt recorded with respect to convertible debt conversion into ordinary shares in conjunction with the Company’s 2019 initial public offering and a $0.7 million change period over period in the fair value adjustments of the warrant liability. These increases were offset by a $3.4 million change in period over period fair value adjustments of the derivative liability associated with the convertible debt, a decrease in interest expense mostly related to the convertible debt of $14.7 million and an increase in interest income of $0.8 million.

Cash Position: Cash and cash equivalents were $50.8 million at December 31, 2019, compared to $10.9 million at December 31, 2018.

Conference Call

Management will host a conference call today at 8:30 am ET to discuss the financial results and provide a general business update. The call can be accessed by dialing (877) 407-0989 or (201) 389-0921 (international) and referencing conference ID 13701108. A live audio webcast of the event can be accessed by visiting the Investors & News section of Stealth’s Investor website, https://investor.stealthbt.com/. A replay of the webcast will be archived on Stealth’s website for 30 days following the event.

On April 1, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported the achievement of key milestones reflecting portfolio-wide progress against the company’s 2020 goals (Press release, Blueprint Medicines, APR 1, 2020, View Source [SID1234556080]). These milestones include the compilation of top-line data for pralsetinib in patients with RET-mutant medullary thyroid cancer (MTC), supporting plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in the second quarter of 2020.

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"As our company and the communities we serve face the COVID-19 pandemic, I am exceptionally proud of our team’s nimbleness and persistency in advancing multiple therapies across our portfolio for the patients who need them," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "I am particularly encouraged that we have advanced pralsetinib toward registration across multiple tumor types and have made strong progress on the avapritinib program, with a compelling dataset in patients with systemic mastocytosis reported last month. The top-line data announced today demonstrate the potential of pralsetinib to be a best-in-class therapy for patients with RET-altered thyroid cancers, with deep and durable responses in both the first-line and relapsed settings."

Top-line Data from Phase 1/2 ARROW Trial in RET-Altered Thyroid Cancers

Top-line results announced today support Blueprint Medicines’ plans to submit an NDA for pralsetinib in patients with RET-mutant MTC previously treated with an approved multi-kinase inhibitor (MKI) in the second quarter of 2020. The registration endpoints are overall response rate (ORR) and duration of response (DOR), based on independent central radiology and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria.

Top-line efficacy data were reported for patients treated with pralsetinib who were evaluable for response assessment per RECIST 1.1, as determined by blinded independent central review. All patients received the proposed indicated dose of 400 mg once daily (QD). All results were as of a data cutoff date of February 13, 2020.

In 53 patients with RET-mutant MTC previously treated with cabozantinib or vandetanib, the ORR was 60 percent (95% CI: 46-74%) with one response pending confirmation. Nearly all patients (98 percent) had tumor shrinkage. The median DOR was not reached (95% CI: not estimable, not estimable), and the 18-month DOR rate was 90 percent (95% CI: 77-100%).

In addition, the top-line data showed robust clinical activity in treatment-naïve patients, supporting the potential of pralsetinib across lines of therapy. In 19 patients with RET-mutant MTC who had not received prior systemic treatment, the confirmed ORR was 74 percent (95% CI: 49-91%), and all patients had tumor shrinkage. The median DOR was not reached (95% CI: 7 months, not estimable), with 12 of 14 responders remaining in response for up to 15 months as of the data cutoff date.

In nine patients with RET fusion-positive thyroid cancer, the confirmed ORR was 89 percent (95% CI: 52-100%), and all patients had tumor shrinkage. The median DOR was not reached (95% CI: 8 months, not estimable), with seven of eight responders remaining in response for up to 20 months as of the data cutoff date.

Top-line safety data were consistent with those previously reported. Pralsetinib was well-tolerated, and most treatment-related adverse events (AEs) were Grade 1 or 2. Across all patients enrolled in the ARROW trial treated at the proposed indicated dose of 400 mg QD (N=438), only 4 percent discontinued treatment with pralsetinib due to treatment-related AEs.

Blueprint Medicines plans to present the full data at a scientific meeting this year.

NDA Submission for Pralsetinib for RET Fusion-Positive NSCLC

Blueprint Medicines completed the rolling NDA submission for pralsetinib for RET fusion-positive non-small cell lung cancer (NSCLC). Blueprint Medicines requested priority review for the application, which, if granted, could result in a six-month review process.

Top-line Data from Phase 3 VOYAGER Trial in Third-Line GIST

Blueprint Medicines plans to lock the VOYAGER trial database in April and provide top-line data to the FDA for avapritinib in third-line gastrointestinal stromal tumor (GIST), to enable the FDA to take action on the proposed fourth-line GIST indication by the May 14, 2020 PDUFA date.

Submission of IND Application for BLU-263

Blueprint Medicines submitted an investigational new drug (IND) application to the FDA for BLU-263, a next-generation KIT inhibitor, for the treatment of patients with indolent systemic mastocytosis (SM). With its drug candidates avapritinib and BLU-263, Blueprint Medicines is pursuing a comprehensive strategy to address a broad population of patients with SM and other mast cell disorders.

About RET-Altered Solid Tumors

RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and MTC. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET alterations are observed at low frequencies in colorectal, breast, pancreatic and other cancers, and RET fusions have been observed in patients with treatment-resistant EGFR-mutant NSCLC.

Currently, there are no approved therapies that selectively target RET-driven cancers, although there are several approved MKIs with RET activity being evaluated in clinical trials. To date, clinical activity attributable to RET inhibition has been uncertain for these approved MKIs, likely due to insufficient inhibition of RET and off-target toxicities. There is a need for precision therapies that provide durable clinical benefit by selectively targeting RET alterations and anticipated resistance mutations.

About Pralsetinib

Pralsetinib is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. Blueprint Medicines is developing pralsetinib for the treatment of patients with RET-altered NSCLC, MTC and other solid tumors. The FDA has granted Breakthrough Therapy Designation to pralsetinib for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy, and RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Pralsetinib was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. In preclinical studies, pralsetinib consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, pralsetinib demonstrated markedly improved selectivity for RET compared to pharmacologically relevant kinases, including approximately 90-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, pralsetinib has the potential to overcome and prevent the emergence of clinical resistance. Blueprint Medicines believes this approach will enable durable clinical responses across a diverse range of RET alterations, with a favorable safety profile.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of pralsetinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for pralsetinib in the rest of the world.