On November 10, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that the company has executed an exclusive license agreement with Leiden University Medical Centre ("LUMC") for a first-in-class ex vivo lentiviral gene therapy for the treatment of RAG1 severe combined immunodeficiency ("RAG1-SCID") (Press release, Mustang Bio, NOV 10, 2021, View Source [SID1234595269]).

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The therapy, which includes low-dose conditioning prior to reinfusion of the patients’ own gene-modified blood stem cells, is currently being evaluated in a Phase 1/2 multicenter clinical trial in Europe. The ongoing clinical trial recently enrolled its first patient, and additional clinical sites are expected to be added in the near future. The RAG1-SCID program has been granted Orphan Drug Designation by the European Medicines Agency.

Mustang also established an ongoing partnership with Frank J. Staal, Ph.D., professor of Molecular Stem Cell Biology and molecular immunologist, whose laboratory developed the therapy. Dr. Staal will continue the development of additional lentiviral gene therapies in his lab, to which Mustang Bio has rights under the agreement.

The RAG1-SCID therapy expands the pipeline of ex vivo lentiviral gene therapies currently in development at Mustang. The Company’s lead programs, MB-107 and MB-207, are being investigated for the treatment of X-linked severe combined immunodeficiency ("XSCID"). A pivotal multicenter trial studying MB-107 is expected to enroll its first patient in the first quarter of 2022. XSCID and RAG1-SCID make up almost 60% of all SCID cases1 combined.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang said, "We are excited to add RAG1-SCID to the Mustang portfolio as it enables us to leverage our lentiviral gene therapy expertise and experience and our state-of-the-art cell processing facility. Mustang is establishing itself as the leader in developing treatments for patients with severe combined immunodeficiency, an area of high unmet need. We have made great progress in moving our XSCID therapy into a registrational trial and look forward to similarly advancing this RAG1-SCID therapy to make it available for patients in need of life-saving treatment."

About RAG1-SCID
Severe combined immunodeficiency (SCID) due to complete recombinase-activating gene-1 (RAG1) deficiency is a rare, genetic severe combined immunodeficiency disorder due to null mutations in the RAG1 gene resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, low or absent serum immunoglobulins, and normal natural killer cell counts. As is the case with other types of SCID, RAG1-SCID is fatal in infancy unless immune reconstitution is achieved with hematopoietic stem cell transplantation (HSCT).

On November 10, 2021 Pharos iBio reported its PHI-501, a next-generation anticancer drug for acute myeloid leukemia (AML), has won orphan drug designation from the U.S. Food and Drug Administration (FDA) (Press release, Pharos iBio, NOV 10, 2021, View Source [SID1234595286]).

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It was the U.S. regulator’s second orphan drug designation of the Korean company’s product. FDA granted similar status to Pharos iBio’s main pipeline, PHI-101, a next-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor for AML, in 2019.

PHI-501 is the first targeted anticancer therapeutics against neuroblastoma-RAS (NRAS) mutation using a more effective method for inhibition using synthetic lethality.

NRAS is a protein that plays a significant role in cell differentiation, proliferation, and survival in acute myeloid leukemia. However, NRAS mutants continuously send signals for cell growth which also leads to cancer growth.

According to Decision Resources Group, a global health industry research firm, AML is a rare disease that shows increased occurrence in the older populations above 65. It is particularly prevalent in the U.S. and Europe. The group expected the global market for AML treatments to reach $2.5 billion by 2025 with a 15 percent annual growth.

Pharos iBio holds eight new drug pipelines, including PHI-101, and originally built big data and AI-based platform technology.

Through open innovations, the company plans to promote joint research and development and technology transfer with global pharmaceutical companies and overseas organizations.

"We will benefit from various incentives, including shortened review period for clinical approval and commercialization, reduced application fee with tax exemption, and a seven-year marketing exclusivity," said Pharos iBio CDO Han Hye-jung, former principal scientist at Roche Sequencing Solutions. "We will speed up the clinical trials of PHI-501 to enter the global market."

The company has recently built a synthesis and bio laboratory at its headquarters in Anyang, Gyeonggi Province, establishing an infrastructure to discover new drug candidates independently.

Pharos iBio received approval for the first phase 1 clinical trial of PHI-101 in Korea and continued to strengthen its ability to develop new drugs for rare and incurable diseases.

On November 10, 2021 Diffusion Pharmaceuticals Inc. (NASDAQ: DFFN) ("Diffusion" or the "Company"), a biopharmaceutical company developing novel therapies that enhance the body’s ability to deliver oxygen to areas where it is needed most, reported financial results for the third quarter of 2021 and provided a business update (Press release, Diffusion Pharmaceuticals, NOV 10, 2021, View Source [SID1234595760]).

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"We believe this is an exciting time for Diffusion Pharmaceuticals. The data we have obtained over the last year from our TCOM and COVID-19 studies have enhanced our understanding of TSC dosing and its mechanism of action, which we feel provides support for the broad potential use of TSC as a treatment for conditions complicated by hypoxia. As the next step in our efforts to realize TSC’s broad potential, we have chosen to target the treatment of hypoxic solid tumors as a first indication," said Robert Cobuzzi, Jr. Ph.D., President and CEO of Diffusion. Dr. Cobuzzi continued, "We believe targeting hypoxic solid tumors is right for TSC given the significant unmet medical need, the compelling preclinical and clinical data accumulated to date, and the current, intravenous formulation of TSC. As a prelude to launching the first clinical study in the program, we plan to obtain input from the U.S. Food and Drug Administration ("FDA") on its design in early 2022, and our study start date will be dependent upon FDA feedback and the availability of clinical drug supply. In the meantime, we will continue to execute on the final two Oxygenation Trials. On that, I am happy to say we plan to dose the first subject in the Altitude Trial within the next couple weeks, and in parallel we are working to initiate the ILD-DLCO Trial."

TSC Development Plans for 2021 and 2022

The Oxygenation Trials

In June 2021, Diffusion reported a positive trend in oxygenation from its Phase 1b TCOM Trial evaluating the effect of TSC versus placebo on peripheral tissue oxygenation in healthy normal volunteers using transcutaneous oxygen measurements. The data obtained from the TCOM Trial have been used to guide dose selection in the Company’s two additional Oxygenation Trials–the Altitude Trial and the ILD-DLCO Trial.

Altitude Trial: This trial will be a double-blind, randomized, placebo-controlled study to evaluate the effects of TSC on maximal oxygen consumption, or VO2, and partial pressure of blood oxygen, or PaO2, in normal healthy volunteers subjected to incremental levels of physical exertion while exposed to hypoxic and hypobaric conditions (i.e., simulated altitude). The study is designed to evaluate the effect of TSC versus placebo on maximal oxygen consumption and partial pressure of blood oxygen. The Company expects dosing of the first subject in the Altitude Trial in November 2021 and expects to complete the study in late December 2021 or early January 2022. The Company anticipates reporting topline results from the Altitude Trial within two months of study completion.

ILD – DLCO Trial: This trial will be a double-blind, randomized, placebo-controlled study which will evaluate the effects of TSC on the diffusion of carbon monoxide through the lungs ("DLCO") in patients with previously diagnosed interstitial lung disease who have a baseline DLCO test result that is abnormal. DLCO will act as a surrogate measure of oxygen transfer efficiency, or uptake, from the alveoli of the lungs, through the plasma, and onto hemoglobin within red blood cells. The study will be statistically powered to evaluate the difference in effect of TSC versus placebo on improvement in DLCO as well as in a standard six-minute walk test. Diffusion anticipates initiating the ILD-DLCO Trial late in the fourth quarter of 2021 and completing the trial in the first quarter of 2022, with topline results reported within two months of study completion.

In addition, with the clearance of the Investigational New Drug application ("IND") to support the ILD-DLCO Trial from the Pulmonary, Allergy, and Critical Care division of the FDA received during the third quarter, Diffusion now has open INDs for TSC with four FDA divisions: Pulmonary, Allergy, and Critical Care; Cardiology and Nephrology, Neurology and Oncology.

The Company believes these Oxygenation Trials remain integral to the overall development plan for TSC, as they are intended to provide further information regarding TSC’s mechanism of action and dose-response characteristics, as well as to support what the Company believes is the broad therapeutic potential of TSC to treat a variety of conditions complicated by hypoxia. More specifically, the Altitude Trial is designed to provide information on TSC’s effects on oxygen consumption, and the ILD-DLCO Trial is designed to evaluate the effects of TSC on the uptake of oxygen through the lungs.

Using TSC to Treat Hypoxic Solid Tumors

While the Company intends to continue developing data to support TSC’s broad potential uses, it has announced that its near-term focus will be the design and execution of a clinical program to support the use of intravenously administered TSC as a treatment for hypoxic solid tumors.

"Solid tumors comprise approximately 90% of all adult cancers, and according to the American Cancer Society, roughly 1.9 million new cancer cases will be diagnosed in the U.S. alone during 2021. Hypoxia is a common complicating factor in nearly all solid tumors, directly contributing to treatment resistance and metastatic potential. Tumor hypoxia has been studied for decades and continues to be an area of unmet need that negatively influences treatment outcomes independent of modality," said Chris Galloway, M.D., Chief Medical Officer of Diffusion. Dr. Galloway went on to state, "We believe TSC’s unique mechanism of action along with its safety profile has the potential to improve treatment success of solid tumors coincident with standard of care therapy. Diffusion has existing pre-clinical and clinical evidence of TSC’s potential positive effects in solid tumors, and now further informative exposure-response data from recently completed studies like the Oxygenation Trials and our COVID-19 trial. Building upon this we are actively working to design a targeted development plan in multiple solid tumor types and plan to submit a briefing document to the FDA in early 2022. In parallel, data from the upcoming Altitude and ILD-DLCO Trials will be used to refine and enhance our understanding of TSC’s dose and effects that conceivably translate into a multitude of oncology and non-oncology indications."

3Q21 Financial Results

Research and development expenses in the third quarter were $2.1 million compared to expenses of $3.1 million in the prior year period, a decrease of $1.0 million. This decrease was attributable to the completion of the Company’s clinical trial evaluating TSC in COVID-19 patients in February and the wind-down of the Company’s glioblastoma multiforme and stroke trials, and partially offset by increased headcount and costs related to the startup of the Altitude and ILD-DLCO Trials.

General and administrative expenses were $1.9 million during the third quarter of 2021 versus $2.1 million in the comparable quarter last year. The decrease compared to the prior year period was primarily attributable to executive separation payments in the prior year period partially offset by increased salaries, wages, stock-based compensation, and professional fees related to increased headcount in 2021.

The Company recognized a non-recurring, non-cash asset impairment charge of $8.6 million during the third quarter of 2021 versus $0.0 in the comparable quarter last year. The charge was related to the full impairment of the in-process research and development asset associated with the Company’s DFN-529 product candidate, which was acquired in January 2016 in connection with the reverse merger of Diffusion Pharmaceuticals LLC and RestorGenex Corporation.

The Company’s third quarter 2021 operating loss was $12.6 million as compared with an operating loss of $5.2 million in the third quarter of 2020, with the increase primarily attributable to the $8.6 million non-cash asset impairment charge described above. Excluding the asset impairment charge, the Company’s operating loss decreased by $1.3 million.

As of Sept 30, 2021, Diffusion had cash and cash equivalents of approximately $40.3 million as compared to $18.5 million as of December 31, 2020. The increase was primarily attributable to the proceeds of the Company’s public offering of common stock in February 2021. Diffusion estimates that it has sufficient cash to fund operations and capital expenditures through 2023.

On November 10, 2021 CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), reported promising data from the completed dose-escalation part of the Phase 1 clinical trial of CV8102, the company’s lead oncology candidate (Press release, CureVac, NOV 10, 2021, View Source [SID1234595052]). The data support the hypothesis that local injection of the RNA immuno-modulator into a single tumor lesion is able to induce a systemic response leading to immune attack against both injected and non-injected tumors. Extensive analysis of immune cell activation shows efficient stimulation of the immune system characterized by the induction of interferon alpha and interferon gamma signaling pathways. Serial tumor biopsies from individual patients demonstrated increased infiltration of tumor-fighting T cells in the microenvironment of injected as well as non-injected tumors. The study focuses on patients with advanced cutaneous melanoma, adenoid cystic carcinoma and squamous cell carcinoma of the skin or head and neck, treated with CV8102 alone and in combination with anti-PD-1 antibodies. The data are being presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference, held in Washington, D.C., and virtually from November 10–14, 2021.

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"The preliminary data from the Phase 1 dose escalation part of this study allow a much deeper understanding of the promising biologic effects of CV8102 observed in several patients," said Dr. Klaus Edvardsen, Chief Development Officer at CureVac. "CV8102 is designed to mimic a viral infection of the injected tumor. This potentially leads to a broad activation of tumor-specific T cells, which can kill tumor cells at the injected but also at distant sites. We expect that the data will be supplemented by upcoming results of the expansion study, which will provide further insight into which patients are more likely to experience a clinical response to CV8102."

An expansion part of the Phase 1 study, initiated in February and fully recruited in October 2021, aims to confirm the safety, tolerability and efficacy of CV8102 at the recommended 600μg dose in patients with advanced melanoma. The study involves 40 trial participants, with 10 in the single-agent cohort and 30 in the combination cohort. Data from the expansion part of the study is expected in the second half of 2022.

The dose-escalation part of the study included a total of 58 patients, 33 of which were treated in the in the single-agent cohort and 25 in the combination cohort. Data presented in September at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) conference found that as of the cutoff date of June 21, 2021, in the single-agent CV8102 dose-escalation cohort, one patient with a complete response and two patients with a partial response were observed. In addition, 12 patients experienced stable disease. In the PD-1 combination dose-escalation cohort, one PD-1 refractory melanoma patient experienced a partial response while three patients experienced stable disease.

About CV8102 and the Phase 1 Clinical Trial

CV8102 is a single-stranded non-coding RNA optimized to maximize activation of cellular receptors that normally detect viral pathogens entering the cells, such as toll-like receptors 7 and 8 (TLR7/8), and retinoic acid inducible gene I (RIG-I), mimicking a viral infection of the tumor. CV8102 is designed to recruit and activate antigen-presenting cells at the site of injection to present tumor antigens released from tumor cells to T cells in the draining lymph node. This potentially leads to activation of tumor-specific T cells, which can kill tumor cells at the injected site, but also at distant non-injected tumor lesions or metastases.

The Phase 1, open-label, dose escalation and expansion study of CV8102 is fully recruited and includes patients with advanced melanoma, cutaneous squamous cell carcinoma, squamous cell carcinoma of head and neck or adenoid cystic carcinoma. The primary objective of the study is to assess safety and tolerability of CV8102.The dose escalation part tests escalating doses of single-agent CV8102 and CV8102 in combination with licensed anti-PD-1 antibodies in the range of 25-900µg. The expansion part of the study focuses on patients with advanced melanoma treated with a recommended dose of 600µg.

On November 10, 2021 F-star Therapeutics, Inc. (NASDAQ: FSTX), a clinical-stage biopharmaceutical company dedicated to developing next generation bispecific immunotherapies to transform the lives of patients with cancer, reported third quarter 2021 financial results and a corporate update (Press release, F-star, NOV 10, 2021, View Source [SID1234595068]).

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Eliot Forster, CEO of F-star Therapeutics, Inc., said, "A year on from listing on NASDAQ, we have delivered on our planned milestones, and through them value for patients, partners and our investors. Our agile, tenacious approach, working with world-leading investigators, continues to further F-star’s mission to bring our unique bispecific antibodies to patients who need them most. We continue to advance four clinical programs, initiate validating partnerships and execute our financial plan. This past quarter included a number of clinical updates and significant new partnerships with AstraZeneca and Janssen Biotech. I’m proud of the team paving the way with huge passion and dedication to make real the promise of next generation immunotherapies."

The Company continues to advance FS118, F-star’s first-in-class bispecific antibody targeting LAG-3 and PD-L1, in checkpoint inhibitor relapsed head and neck cancer and in checkpoint inhibitor naïve patients with non-small cell lung cancer (NSCLC) and diffuse large B cell lymphoma (DLBCL), with a clinical trial in the latter two populations currently being initiated. FS120, F-star’s first-in-class dual-agonist, bispecific antibody targeting CD137 and OX40, remains on track in the clinic, having completed the accelerated dose titration phase, with presentations at ESMO (Free ESMO Whitepaper) 2021 and SITC (Free SITC Whitepaper) 2021. SB 11285, a second-generation STimulator of INterferon Gene (STING) agonist, continues to advance well in the clinic, further to the update provided in the second quarter of 2021. FS222, the potentially best-in-class bispecific targeting PD-L1 and CD137, is also progressing well in the clinic.

The Company also announced during the third quarter significant new partnerships with both AstraZeneca PLC and Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, leveraging our platform technology. With four clinical-stage programs in progress, F-star is focused on the further development of its wholly-owned pipeline of tetravalent bispecific antibodies, as well as collaborations that have the potential to bring value to shareholders and patients alike.

THIRD QUARTER 2021 AND RECENT HIGHLIGHTS

FS118 development expanded following external clinical validation of the LAG-3 target: The expansion of the FS118 clinical development into checkpoint naïve, biomarker enriched NSCLC and DLBCL patients will broaden the clinical reach of this exciting LAG-3 & PD-L1 targeting bispecific antibody. This adds to the already ongoing checkpoint inhibitor relapsed head and neck cancer study that is anticipated to report data in mid-2022.

Combination of FS120 with KEYTRUDA: In August, F-star announced a clinical trial collaboration and supply agreement with Merck & Co., Inc., Kenilworth, NJ, USA (MSD) to evaluate the combination of FS120, F-star’s first-in-class dual-agonist bispecific antibody targeting CD137 and OX40, with KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy. FS120 has completed the accelerated dose titration phase in monotherapy with no safety concerns identified, and the pharmacokinetics were in line with expectations. The Company continues dose escalation to determine an optimal dosing regimen to initiate the KEYTRUDA combination.

AstraZeneca licenses STING inhibitors: In July, F-star entered into an exclusive licensing agreement with AstraZeneca plc under which AstraZeneca received global rights to research, develop and commercialize next generation STING inhibitor compounds. AstraZeneca was granted exclusive access to F-star’s novel preclinical STING inhibitors and will be responsible for all future research, development and commercialization of the STING inhibitor compounds. This forms part of the second CVR agreement with the former shareholders of Spring Bank Pharmaceuticals, Inc. (Spring Bank). F-star retains rights to all STING agonists currently in clinical development for patients with cancer.

SB 11285 Phase 1 interim update: In July, F-star provided an interim update on the safety, tolerability and pharmacokinetics of its intravenously administered novel STING agonist, alone and in combination with atezolizumab. SB 11285 appeared to be well tolerated both alone and in combination across all dose levels tested to-date, including five dose levels as monotherapy and three dose levels as a combination. The Part 1a/1b study database lock (as defined in the first CVR agreement with Spring Bank’s former shareholders) has been completed. Based on the positive emerging clinical data, further dose escalations are ongoing, and a further clinical update is planned for the second half of 2022.

Johnson and Johnson licenses five new programs, based on platform technology: Under the terms of the license and collaboration agreement, F-star will grant Janssen Biotech a worldwide, exclusive royalty-bearing license to research, develop, and commercialize up to five novel bispecific antibodies directed to Janssen therapeutic targets using F-star’s proprietary Fcab and mAb2 platforms. Janssen will be responsible for all research, development, and commercialization activities under the agreement.

THIRD QUARTER 2021 FINANCIAL SUMMARY

Cash and cash equivalents as of September 30, 2021, were $71.1 million, compared to $18.5 million as of December 31, 2020. The up-front payment of $17.5 million in connection with the license and collaboration agreement with Janssen Biotech is expected to be received in the fourth quarter of 2021.

Research & Development (R&D) expenses were $5.1 million for the quarter ended September 30, 2021, compared to $5.3 million for the corresponding quarter in 2020, which included non-cash stock-based compensation expense of $1.1 million and $1.1 million, respectively.

General & Administrative (G&A) expenses were $5.2 million for the quarter ended September 30, 2021, compared to $7.3 million for the third quarter of 2020, which included non-cash stock-based compensation expense of $0.4 million and $59,000, respectively.

Net loss was $10.8 million, or a loss per share of $0.52 (basic and diluted), for the quarter ended September 30, 2021, compared to a net loss of $3.5 million, or a loss per share of $1.88 (basic and diluted), for the quarter ended September 30, 2020.

CONFERENCE CALL AND WEBCAST
F-star will host a conference call today, November 10, 2021, beginning at 9:00 a.m. EST.

To access the call, participants may join via a live webcast on the Investors & News section of the F-star Therapeutics website, under Events and Presentations. To join by phone, participants may dial the following numbers at least 10 minutes prior to the start of the call:

A replay of the conference call will be available for 90 days from the date of the call and may be accessed in the Investors & News section of the F-star Therapeutics website under Events and Presentations.