On March 26, 2020 Pulmatrix, Inc. (NASDAQ: PULM), a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary and non-pulmonary disease using its patented iSPERSE technology reported its 2019 financial results and provides a business update (Press release, Pulmatrix, MAR 26, 2020, View Source [SID1234555886]).

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"2019 was a transformative year at Pulmatrix marked by significant clinical and corporate milestones," said Ted Raad, Chief Executive Officer of Pulmatrix. "We built significant momentum with regulatory accomplishments, strategic partnerships expanding our global reach, and most importantly, the advancement of both Pulmazole and PUR1800 programs. Our PUR1800 licensing agreement with the Lung Cancer Initiative at Johnson & Johnson and Pulmazole strategic partnership with Cipla Technologies LLC demonstrate the strength of Pulmatrix’s iSPERSE platform to enhance the safety and efficacy of promising drug candidates and we are thrilled to be collaborating with these leading, global partners."

Mr. Raad continued, "On the clinical front, we initiated our ongoing Phase 2 clinical study of Pulmazole for the treatment of ABPA, which we believe has the potential to change the standard of care for patients with asthma and ABPA. In collaboration with Johnson & Johnson, we plan to initiate the PUR1800 Ph1b clinical study and chronic toxicology studies in mid-2020. In parallel, we are working to advance a new proprietary iSPERSE enabled 505(b)(2) program into the clinic in 2021. However, the novel coronavirus may adversely impact the planned timelines for each of these trials should institutions need to suspend enrollments or should we voluntarily suspend enrollment at sites due to risks related to the coronavirus. We will evaluate these issues on an ongoing basis."

2019 and Recent Highlights:

Initiated Phase 2 trial evaluating Pulmazole, an inhaled iSPERSE formulation of the antifungal itraconazole, for the treatment of Allergic Bronchopulmonary Aspergillosis ("ABPA") in patients with asthma.
Announced kinase inhibitor licensing and development agreement with the Lung Cancer Initiative at Johnson & Johnson. The agreement provides the Lung Cancer Initiative option to access a portfolio of narrow spectrum kinase inhibitors intended for development in lung cancer interception. Under the terms of the agreement, Pulmatrix received a $7.2M upfront payment with eligibility for additional milestone and royalty payments.
Entered into strategic partnership with Cipla Technologies LLC ("Cipla") for the worldwide development and commercialization of Pulmazole. Under the terms of the partnership, Pulmatrix received a $22M upfront payment, fully funding the Phase 2 study. The partnership leverages Cipla’s expertise in respiratory drug development and global commercialization capability and footprint (the "Cipla collaboration").
Received U.S. FDA Fast Track designation for Pulmazole for the treatment of ABPA.
Strengthened intellectual property portfolio with issuance of US patent covering iSPERSE formulations for Pulmazole.
Announced research collaboration with Nocion Therapeutics to explore inhaled drug delivery technologies.
Completed $16.6M public offering extending cash runway through data for ongoing Pulmazole Phase 2 program.
Strengthened Board of Directors with appointment of life sciences executive Rick Batycky.
Financials

As of December 31, 2019, Pulmatrix had $23.4 million in cash and cash equivalents, compared to $2.6 million for the year ended December 31, 2018.

Revenue for 2019 was $7.9 million, compared to $0.2 million for 2018. The increase was the result of the recognition of revenue pursuant to the Cipla Collaboration.

Research and development expense was $12.8 million in 2019 compared to $13.0 million in 2018. The decrease year–over–year was primarily due to decreased spend of $1.6 million in employment costs as a result of decreased share based compensation expense and $0.6 million on the PUR1800 project as a result of the completion of a pre-clinical toxicology study in 2018, partially offset by increased spend of $2.0 million on the Pulmazole project.

General and administrative expense was $8.5 million for 2019 and $7.5 million for 2018. The increase year-over-year was due to a $0.3 million royalty payment made to the Cystic Fibrosis Foundation which resulted from the Cipla Collaboration and increases of $0.3 million of legal and patent costs, $0.2 million of employment costs and $0.2 million in professional consulting expense.

Goodwill had an impairment charge of $7.3 million in 2019 compared to a $0.1 million charge in 2018.

Net loss for 2019 and 2018 were both $20.6 million. The net loss in 2019 was primarily attributable to spend on the Pulmazole project as we advance our Phase 2b clinical study and PUR1800 manufacturing costs for the upcoming Phase 1b clinical study.

On March 26, 2020 CG Oncology, Inc. has reported an exclusive license, development and commercialization agreement with Kissei Pharmaceutical Co., Ltd. ("Kissei") for its oncolytic immunotherapy drug CG0070 for Japan, South Korea, Taiwan and other Asian countries with the exception of China (Press release, Cold Genesys, MAR 26, 2020, View Source [SID1234555885]). CG Oncology has completed an investigational Phase 2 study of CG0070 in the United States in patients with BCG-unresponsive, non-muscle-invasive bladder cancer (NMIBC). In addition, CG Oncology is studying the use of CG0070 in combination with immune checkpoint inhibitors in bladder cancer and other solid tumors.

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"We are very excited to partner with Kissei, an R&D-oriented Japanese pharmaceutical company that shares our interests in developing innovative medicines for patients with debilitating urological and oncology conditions," said Arthur Kuan, CEO of CG Oncology. "Kissei possesses a track record of commercial success with both in-licensed and proprietary therapies in Asian markets, and their dedication to develop CG0070 in these territories makes Kissei an ideal partner. We sincerely look forward to collaborating with them to accelerate the development of CG0070 and to globalize patient access to a potentially important new therapeutic."

Under the terms of this agreement, CG Oncology receives a licensing fee of $10 million in cash, with the potential for an additional $100 million in development and commercial milestone payments, and will receive certain royalties on sales of CG0070 in the territories licensed by Kissei. CG Oncology also receives a $30 million equity investment from Kissei. Further financial details of the agreement were not disclosed.

"Through our extensive experience with in-licensed and proprietary therapies, we have strong expertise to successfully develop and commercialize CG0070 in Japan, and other countries," said Mutsuo Kanzawa, Chairman and CEO of Kissei. "We look forward to collaborating closely with CG Oncology to address the significant unmet medical needs of patients with this innovative medication."

About CG0070

CG0070, a selectively replicative oncolytic immunotherapy based on a modified adenovirus type 5 backbone that contains a cancer-selective promoter and a GM-CSF transgene, destroys bladder tumor cells through their defective retinoblastoma (Rb) pathway. CG0070 was designed to work in two complementary ways. First, it replicates inside the tumor’s cells with dysfunctional Rb pathways, causing tumor cell lysis and immunogenic cell death. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, which can stimulate a systemic anti-tumor immune response that involves the body’s own white blood cells. In advanced clinical studies, CG0070 has been shown to be a safe and efficacious agent in NMIBC following BCG failure. The scientific rationale and clinical results to date of CG0070 make it a promising agent to be developed for a variety of solid tumor types to be used alone or in combination with immune checkpoint inhibitors.

On March 26, 2020 EpiVax Oncology, Inc., a precision cancer immunotherapy company, reported it has reduced the timeline from biopsy to vaccine to under 4 weeks for its personalized neoantigen therapeutic cancer vaccines (Press release, EpiVax, MAR 26, 2020, View Source [SID1234555884]).

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CEO and Co-Founder, Gad Berdugo, MSc Eng., MBA, stated, "This is a real game changer for personalized cancer vaccines. It will enable our precision immunotherapy to treat patients in the neoadjuvant clinical setting before surgical removal of their tumors, potentially improving the patient’s clinical outcome."

Dominique Bridon, PhD, CTO said, "Personalized cancer vaccines are created based on information obtained from an individual’s tumor. Previously, the process to create an a personalized vaccine starting from tumor biopsy took at least 12 to 18 weeks. We expect that reducing this time to less than 4 weeks will improve the effectiveness of our personalized vaccine candidates in attacking the tumor."

Arjun Balar, MD, Associate Professor of Medicine, Director Genitourinary Medical Oncology Program, NYU Laura and Isaac Perlmutter Cancer Center, NYU Langone Health said, "The ability to generate a vaccine that is ready for use in a patient in under 4 weeks is a critical advancement. Patients with metastatic disease cannot wait for effective therapy. Moreover, a rapid biopsy to vaccine administration time opens the door to presurgical or neoadjuvant "window of opportunity" studies. These studies will definitively address the biological effects of a personalized cancer vaccine in the tumor-microenviornment. This is something that has long been missing in previous approaches to cancer vaccines."

Gary D Steinberg, MD, Professor of Urology, Director Bladder Cancer program, NYU Langone Health stated, "High grade bladder cancer is an aggressive disease that will progress and metastasize to other parts of the body. Thus, therapeutic interventions need to be provided in a timely fashion without unnecessary delay. With a personalized cancer vaccine process under 4 weeks, we can safely create a vaccine to treat all stages of aggressive cancer including in the neoadjuvant, adjuvant and metastatic setting. Ideally, we will also be able to treat patients with high grade non-muscle invasive cancer. This is a significant advance in the armamentarium of newly developed treatments for this cancer which kills over 17,000 people per year in the US."

Epivax Oncology’s neopeptides are patient specific peptides that are designed using Ancer: EpiVax Oncology’s advanced in-silico neoantigen prediction platform powered by machine learning based algorithms that have been refined over more than 20 years by Providence-based EpiVax Inc.

On March 26, 2020 CEL-SCI Corporation (NYSE American: CVM), a Phase 3 cancer immunotherapy company, reported the closing of the offering of 630,500 shares of its common stock at a price of $12.22 per share, for total gross proceeds of approximately $7.7 million, before deducting underwriting discounts and other offering expenses payable by the Company (Press release, Cel-Sci, MAR 26, 2020, View Source [SID1234555883]). Additionally, the Company has granted the underwriter a 45-day option to purchase up to 94,575 additional shares to cover over-allotments.

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Aegis Capital Corp. acted as the sole book-running manager for the offering.

This offering was made pursuant to a "shelf" registration statement on Form S-3 (File No. 333-226558) filed with the Securities and Exchange Commission (SEC). A prospectus supplement and accompanying base prospectus relating to the offering were filed with the SEC and are available on the SEC’s website at View Source and may be obtained from Aegis Capital Corp., Attention: Syndicate Department, 810 7th Avenue, 18th floor, New York, NY 10019, by email at [email protected], or by telephone at (212) 813-1010.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On March 26, 2020 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported the publication in the peer-reviewed journal Science Translational Medicine of preclinical data that established the therapeutic rationale for evaluating a potent and highly selective inhibitor of transforming growth factor-beta 1 (TGFβ1) activation to overcome primary resistance to checkpoint inhibitor therapy (Press release, Scholar Rock, MAR 26, 2020, View Source [SID1234555882]).

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"With this publication, we are sharing the strong body of preclinical evidence we have built supporting the clinically-derived rationale for evaluating TGFβ1’s key role in primary resistance to checkpoint inhibitor therapy and the potential of a highly specific inhibitor of TGFβ1 activation to overcome this challenge. In the second half of this year, we may gain early insights from our Phase 1 proof-of-concept trial in patients with solid tumors on SRK-181’s potential to overcome the immune exclusion that we believe leads to primary resistance to anti-PD-(L)1 therapy," said Alan Buckler, Ph.D., Chief Scientific Officer of Scholar Rock. "Moreover, these published data provide further validation of Scholar Rock’s proprietary platform to develop antibodies that locally and selectively target the precursor form of growth factors with the aim of avoiding the dose-limiting toxicities that have hindered traditional approaches to targeting growth factors."

The introduction of immunotherapy, including checkpoint inhibitor therapy, has revolutionized the treatment of a wide variety of cancers, delivering profound and durable responses for many patients. Unfortunately, this therapeutic approach is only effective in a small subset of patients; even at the outset of treatment, some tumors show primary resistance to anti-PD-(L)1. Human tumor profiling and several preclinical studies have implicated TGFβ signaling activity as a potential point of intervention to overcome primary resistance to checkpoint inhibition. However, the development of therapies targeting TGFβ signaling has been hindered by dose-limiting cardiotoxicities, potentially due to non-selective inhibition of multiple TGFβ isoforms.

As detailed in the Science Translational Medicine publication "Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape," SRK-181 inhibits TGFβ1 activation with high selectivity and has demonstrated in preclinical studies the potential to overcome primary resistance and meaningfully expand the number of patients who could benefit from checkpoint inhibitor therapy. (Martin et al., Sci. Transl. Med. 12: 25 March 2020)

Based on RNAseq data from the Cancer Genome Atlas (TCGA), TGFβ1 is the most prevalent isoform expressed in the majority of human cancer types, with the exception of breast cancer, mesothelioma, and prostate cancer, where TGFβ3 is also expressed. This finding was also observed in examination of individual samples.
TGFβ1 is likely expressed by multiple cell types within the tumor microenvironment and each cell type produces TGFβ1 in different large latent complexes (LLCs). This is supported by TCGA data, which indicates essentially all tumor types express mRNA encoding all four LLC-presenting molecules, namely LTBP1, LTBP3, GARP, and LRRC33. By targeting the precursor form of TGFβ1, SRK-181 achieves exquisite isoform specificity, inhibiting latent TGFβ1 activation in all known molecular contexts without binding to latent TGFβ2, latent TGFβ3, or any of the three active TGFβ growth factors.
Scholar Rock identified three syngeneic mouse tumor models that recapitulate key features of human primary resistance to checkpoint inhibitor therapy: MBT-2 (bladder cancer), Cloudman S91 (melanoma) and the EMT-6 (breast cancer) mouse models. Combination treatment with SRK-181-mIgG1 and an anti-PD-1 therapy resulted in tumor regression or control and survival benefit across these three identified cancer models. This tumor response was also shown to be durable, where mice with no measurable tumor at treatment cessation remained tumor free.

MBT-2 bladder
cancer model
(Response**: %, N)

Cloudman S91
melanoma model
(Response***: %, N)

EMT-6 breast
cancer model
(Response*: %, N)

Control

0% (0/12)

0% (0/11)

0% (0/9)

Anti-PD1 monotherapy

0% (0/13)

25% (3/12)

0% (0/9)

SRK-181-mIgG1 monotherapy

0% (0/12)

0% (0/12)

0% (0/10)

Anti-PD-1/SRK-181-mIgG1, 3 mg/kg

29% (4/14)

75% (9/12)

NT

Anti-PD-1/SRK-181-mIgG1, 10 mg/kg

57% (8/14)

44% (4/9)

50% (5/10)

Anti-PD-1/SRK-181-mIgG1, 30 mg/kg

NT

73% (8/11)

NT

* For EMT-6: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 2,000mm3 survival threshold.
** For MBT-2: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 1,200mm3 survival threshold.
*** For Cloudman S91: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 2,000mm3 survival threshold.
NT: Not tested

The tumor regression and control demonstrated in the EMT-6 breast cancer model, which expresses both TGFβ1 and TGFβ3, suggest TGFβ1 is the key isoform contributing to checkpoint resistance and highlights the possibility that selective TGFβ1 inhibition may have therapeutic potential in overcoming primary resistance across a broad spectrum of cancers, irrespective of the expression of other TGFβ isoforms.
Dose-limiting cardiotoxicities have challenged the therapeutic development of TGFβ pathway inhibitors. Selective inhibition of latent TGFβ1 activation with SRK-181 has demonstrated an improved safety profile as compared to pan-TGFβ inhibitors. In a 4-week repeat-dose rat toxicology study, the no-observed-adverse-effect-level (NOAEL) was the highest dose tested of 100 mg/kg once weekly, which is well above the doses necessary to elicit robust anti-tumor responses when combined with anti-PD-1 antibody.
Following combination treatment with SRK-181-mIgG1 and anti-PD-1, there were significant increases in intratumoral effector T cells and decreases in immunosuppressive myeloid cells, suggesting TGFβ1’s multiple contributions to primary resistance to checkpoint inhibition.
Overall percentage of the CD45+ immune compartment did not change.
Ten-fold increase in CD8 T cell representation (average of 34% vs. control average of 3.5%). Single-agent treatment with anti-PD-1 or SRK-181-mIgG1 only resulted in modest increases that did not reach significance in the study.
Significant reduction in immunosuppressive M2-like macrophages (14% vs. control average of 47%) and myeloid-derived suppressor cells (MDSC; 1.4% vs. control average of 10.9%).
About SRK-181

SRK-181 is a potent and highly selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to anti-PD-(L)1 therapy, TGFβ1 is implicated as a key contributor to exclude immune cell entry into the tumor microenvironment, thereby preventing normal immune function. By overcoming this immune cell exclusion, Scholar Rock believes SRK-181 has the potential to induce tumor regression when administered in combination with anti-PD-(L)1 therapy. A Phase 1 proof-of-concept clinical trial in patients with locally advanced or metastatic solid tumors is ongoing. The effectiveness and safety of SRK-181 have not been established and SRK-181 has not been approved for any use by the FDA or any other regulatory agency.