On August 13, 2019 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer, autoimmune/inflammatory, and other diseases, reported financial results for the second quarter ended June 30, 2019 (Press release, Alpine Immune Sciences, AUG 13, 2019, View Source [SID1234538631]).

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"I am proud of the progress Alpine has made in the first six months of the year and the momentum we’ve built heading into a potentially transformative year ahead," said Mitchell H. Gold, MD, Executive Chairman and Chief Executive Officer of Alpine. "The Phase I trial of ALPN-101 in healthy volunteers has advanced through the single-ascending dose cohorts, enabling initiation of the multiple-ascending dose cohorts. This is an important milestone for our first-in-class dual ICOS/CD28 blocker which we believe has the potential to deliver meaningful remissions in inflammatory diseases. We expect to have completed the critical portions of the Phase 1 trial of ALPN-101 by the end of 2019 and look forward to initiating our studies in acute GVHD and Psoriatic Arthritis."

Recent Pipeline and Company Highlights

ALPN-101 Update:

Phase I Trial Successfully Progresses Through the Single-Ascending Dose (SAD) Cohorts: Dosing of all planned SAD cohorts in the Phase I healthy volunteer study has been successfully completed. Enrollment has begun on the multiple-ascending dose cohorts.
"The safety, pharmacokinetic and pharmacodynamic data so far have been encouraging and we believe this study, once complete, will allow us to select an appropriate dose(s) for Phase II studies," said Stanford Peng, MD, PhD, Alpine’s President and Head of Research and Development. "We expect to have these data before the end of the year and hope to present the data publicly in the first half of 2020."

Trials in patients with GVHD and Psoriatic Arthritis are on track to begin following completion of the Phase I healthy volunteer study.
Alpine plans to present additional preclinical data supporting the potential role of ALPN-101 in additional indications at an upcoming scientific conference in the fourth quarter of 2019, supporting the potential broad utility of ALPN-101.
ALPN-202 Update:

Alpine anticipates submitting for regulatory authorization to begin clinical trials by the end of 2019. Alpine believes ALPN-202 will be the first clinical trial of a conditional T-cell agonist targeting CD28 while also providing checkpoint blockade.
Alpine expects to present new mechanistic data in the fourth quarter of 2019 supporting the unique mechanism of action of ALPN-202.
Corporate Update:

Initiated New Collaboration with Adaptimmune: Alpine entered into a collaboration and license agreement with Adaptimmune Therapeutics (NASDAQ:ADAP) in May 2019. The new partnership aims to utilize Alpine’s secreted and transmembrane immunomodulatory protein (termed SIP and TIP) technology in an effort to further enhance the design and development of Adaptimmune’s next-generation SPEAR T-cell therapies.
Expanded Management Team:

Alpine announced the addition of Wayne Gombotz, PhD as Chief Technology Officer of Alpine. With over 30 years of biotechnology and pharmaceutical experience, most recently as Chief Development Officer at Immune Design, Dr. Gombotz will help advance Alpine’s programs into and through each stage of clinical development.

Remy Durand, PhD was also appointed as Vice President, Business Development during the second quarter of 2019. Remy brings with him deep experience in biotechnology strategy, company formation, and investor relations. Prior to joining Alpine, Remy was a Vice President on the investment team at Frazier Healthcare Partners. He received his PhD from Stanford University in Bioengineering.

Financial Results for Second Quarter and First Six Months of 2019

As of June 30, 2019, Alpine had cash, cash equivalents, and short-term investments totaling $55.6 million compared to $52.3 million as of December 31, 2018. Alpine recorded a net loss of $11.9 million and $7.9 million for the three months ended June 30, 2019 and 2018, respectively, and $24.2 million and $13.2 million for the six months ended June 30, 2019 and 2018, respectively.

Research and development expenses for the second quarter ended June 30, 2019 were $10.2 million compared to $5.7 million for the second quarter ended June 30, 2018. For the six months ended June 30, 2019 and 2018, research and development expenses were $20.5 million and $9.5 million, respectively. The company expects a continued increase to research and development activities to support the clinical advancement of its ALPN-101 and ALPN-202 programs.

General and administrative expenses for the second quarter ended June 30, 2019 were $2.6 million compared to $1.9 million for the second quarter ended June 30, 2018. For the six months ended June 30, 2019 and 2018, general and administration expenses were $4.9 million and $4.0 million, respectively. The increase was primarily attributable to professional and legal fees, in addition to personnel-related expenses and the costs associated with expanding the company’s operations as we continue to increase development and clinical activities.

Cash Guidance

Alpine expects to have sufficient cash to fund operations and drive the clinical advancement of Alpine’s lead programs, ALPN-101 in autoimmune/inflammatory diseases and ALPN-202 in oncology, into 2021.

On August 13, 2019, Synlogic, Inc. (the "Company") presented its investor presentation (Presentation, Synlogic, AUG 13, 2019, View Source [SID1234538628]).

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On August 13, 2019 ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, reported its operational and financial results for the three and six months ended June 30, 2019 (Press release, ProMIS Neurosciences, AUG 13, 2019, View Source [SID1234538627]).

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"Over the course of the first half of 2019, the breadth and depth of our unique discovery and development platform was further evidenced as ProMIS made considerable progress in expanding its portfolio of opportunities in neurodegenerative diseases," stated Eugene Williams, ProMIS’ Executive Chairman. "In the second quarter of this year, we were able to identify novel antibodies for Alzheimer’s disease (AD) with selectivity for the neurotoxic form of tau. This is in addition to the prior identification of antibody candidates selectively targeting toxic forms of alpha-synuclein (α-syn) for Parkinson’s disease (PD) and toxic, aggregated forms of TDP43 for amyotrophic lateral sclerosis (ALS)."

Narrated updates relating to ProMIS’ unique approach and capabilities can be found on the ProMIS website by clicking on the links below:

Click here for Chief Medical Officer Dr. James Kupiec’s update on demonstrating early proof-of-concept with biomarkers and focused patient populations
Click here for Chief Scientific Officer Dr. Neil Cashman’s overview of ProMIS’ unique capability to design and develop antibodies selectively targeting toxic misfolded proteins that are a root cause of neurodegenerative diseases
Click here for Chief Development Officer, Dr. Johanne Kaplan’s podium presentation at the Alzheimer’s Association International Conference (AAIC) 2019 showing selective targeting of toxic oligomers by PMN310, a monoclonal antibody rationally designed for greater therapeutic potency in AD
Corporate Highlights

In June 2019, the Company completed a private placement of 4,680,000 common share units at a price of $0.25 per unit resulting in gross proceeds of approximately $1,170,000 ($1,093,492 net of share issuance costs). Each unit consisted of one common share and one common share warrant. The common shares are subject to a four-month hold period from the date of issuance. Each warrant is exercisable into one common share at a price of $0.35 per share at any time for five years.
In May 2019, ProMIS announced the identification of novel antibodies for AD with selectivity for the neurotoxic form of tau. ProMIS leveraged its proprietary drug discovery and development platform to identify several novel antibodies that selectively bind toxic oligomers of tau. The platform produced antibodies that meet a key success factor for a viable Alzheimer’s disease therapy: the ability to selectively target the neurotoxic form of a protein, while sparing the normal forms of the protein, a challenge that has contributed to recent late-stage clinical trial failures. The platform not only generates high-quality antibody candidates, it delivers powerful, validated candidates in months versus years. Used in combination with new biomarkers for Alzheimer’s disease, researchers could dramatically improve the success and speed of future therapy development efforts.
In June 2019, ProMIS presented key data on monoclonal antibody PMN310 for AD at the Keystone Symposium on Neurodegenerative Diseases: New Insights and Therapeutic Opportunities. For nearly fifty years, the conference has attracted the world’s most accomplished researchers in neurodegenerative diseases to discuss future directions in therapy and care. ProMIS Chief Development Officer Dr. Johanne Kaplan presented data showing that PMN310 possesses superior selectivity for amyloid beta toxic oligomers and improved therapeutic potential compared with other amyloid beta-directed antibodies.
Scientific Advisory Board Appointment
In June 2019, the Company appointed C. Warren Olanow, MD, FRCPC, FAAN, FRCP(Hon) to its scientific advisory board (SAB). Dr. Olanow has dedicated his career to the study of neurodegeneration, particularly Parkinson’s disease, through his work in academia, scientific research, clinical trials and professional societies. He is the previous Henry P. and Georgette Goldschmidt Professor and Chairman of the Department of Neurology at the Mount Sinai School of Medicine in New York City and is presently Professor Emeritus in the Department of Neurology and in the Department of Neuroscience. He also serves as Chief Executive Officer of CLINTREX, a pharmaceutical advisory firm that has designed numerous clinical trials in neurodegenerative disease for the pharmaceutical industry.

Financial Results

Results of Operations – Three months ended June 30, 2019 and 2018

Net loss for the three months ended June 30, 2019 was $1,858,530, compared to a net loss of $2,214,861 for the three months ended June 30, 2018, respectively. Included in the net loss amount for the three months ended June 30, 2019 were non-cash expenses of $153,461, representing share-based compensation and amortization of an intangible asset, compared to $173,544 for the three months ended June 30, 2018. The decrease in the net loss in the three months ended June 30, 2019 reflects a decrease in costs associated with external contract research organizations for internal programs, patent costs and share-based compensation offset by increased consultant salaries and associated costs and general corporate expenditures.

Research and development expenses for the three months ended June 30, 2019 were $1,042,618, as compared to $1,531,075 in the three months ended June 30, 2018. The decrease in research and development expense for the three months ended June 30, 2019 is primarily attributed to decreased costs associated external contract research organizations for internal programs and patent costs offset by higher contracted research salaries and associated costs, and higher share-based compensation.

General and administrative expenses for the three months ended June 30, 2019 were $815,937, as compared to $683,786 in the three months ended June 30, 2018. The increase in general and administrative expense for the three months ended June 30, 2019 is primarily attributable to increased consultant salaries and associated costs and general corporate expenditures offset by decreased share-based compensation.

Results of Operations – Six months ended June 30, 2019 and 2018

Net loss for the six months ended June 30, 2019 was $4,305,107, compared to a net loss of $3,771,733 for the six months ended June 30, 2018, respectively. Included in the net loss amount for the six months ended June 30, 2019 were non-cash expenses of $417,334, representing share-based compensation and amortization of an intangible asset, compared to $502,555 for the six months ended June 30, 2018. The increase in the net loss in the six months ended June 30, 2019 reflects the costs associated with operating the Company’s AD therapeutics program, increased contracted research and consultant salaries and associated costs and general corporate expenditures.

Research and development expenses for the six months ended June 30, 2019 were $2,813,271, as compared to $2,229,082 in the six months ended June 30, 2018. The increase in research and development expense for the six months ended June 30, 2019 is primarily attributed to increased spending on external contract research organizations for internal programs, higher contracted research salaries and associated costs, and higher share-based compensation offset by reduced patent costs.

General and administrative expenses for the six months ended June 30, 2019 were $1,491,861, as compared to $1,542,656 in the six months ended June 30, 2018. The decrease in general and administrative expense for the six months ended June 30, 2019 is primarily attributable to decreased share-based compensation offset by increased consultant salaries and associated costs, general corporate expenditures and foreign exchange.

Outlook

The Company will continue to build on its unique, proprietary discovery and development platform to further characterize the potential benefits of its programs selectively targeting toxic aggregates of TDP43 and SOD1 in ALS, toxic forms of α-syn in PD and other α-syn-related disorders, and toxic forms of tau and amyloid beta in AD and other dementias to further support ongoing pharmaceutical partnering discussions.

On August 13, 2019 CStone Pharmaceuticals ("CStone", HKEX: 2616) reported the dosing of the first patient in China for the Phase I registrational study of BLU-667, which was discovered by the company’s partner Blueprint Medicines (Press release, CStone Pharmaceauticals, AUG 13, 2019, View Source [SID1234538606]). This clinical trial is a part of the ongoing, global Phase I ARROW trial that is designed to evaluate the overall response rate (ORR), duration of response, pharmacokinetics, pharmacodynamics and safety of BLU-667 in patients with RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other advanced solid tumors.

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Among all malignant tumors, lung cancer has the highest incidence and mortality rates in the world. Due to heightened risk factors such as pollution and the prevalence of smoking in China, there are approximately 730,000 new cases of lung cancer and 610,000 lung cancer-related deaths reported in China each year[1]. NSCLC accounts for 80-85% of all lung cancers and RET fusions occur in approximately 1-2% of all NSCLC cases. Both platinum-based chemotherapy, the standard first-line treatment for RET-fusion NSCLC, and the second-line treatment of cytotoxic drugs or immune checkpoint inhibitor-based monotherapies offer limited efficacy. As a result, patients experience significant physical and psychological burdens and a lower quality of life.

Thyroid cancer is the most common type of endocrine cancer, and has shown rising incidence rates in recent years. There are approximately 90,000 new cases of thyroid cancer and 6,800 thyroid cancer-related deaths in China each year[1]. MTC accounts for 2-5% of all thyroid cancers, and RET mutations occur in nearly all hereditary MTC patients and approximately 50% of all sporadic MTC patients[2]. Currently there is no effective standard of care treatment approved for MTC patients in China.

BLU-667 is an orally available, highly selective and potent RET inhibitor. In June 2018, CStone obtained exclusive rights from Blueprint Medicines to develop and commercialize three therapeutic candidates, including BLU-667, in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights to the three therapeutic candidates in the rest of the world.

In June 2019, Blueprint Medicines reported updated results from the ARROW clinical trial. BLU-667 showed durable anti-tumor activity regardless of RET-altered tumor type and was well-tolerated. As of the data cutoff date of April 28, 2019:

In 35 evaluable patients previously treated with platinum-based chemotherapy[3]. BLU-667 demonstrated an ORR of 60% (one complete response and 20 partial responses (PR); all responses were confirmed) and a disease control rate (DCR) of 100%.
In 16 evaluable RET-mutant MTC patients previously treated with cabozantinib or vandetanib, BLU-667 demonstrated an ORR of 63% (nine confirmed PRs, one PR pending confirmation) and a DCR of 94%[4] .
These patients with RET-fusion NSCLC and RET-mutant MTC received a starting dose of 400 mg once daily, which is the recommended Phase 2 dose. Across all patients, BLU-667 was well-tolerated and most adverse events reported by investigators were Grade 1 or 2.
Dr. Frank Jiang, Chairman and CEO of CStone, commented: "In China, lung cancer has the highest incidence rate and mortality rate among all malignancies. BLU-667 is an agent with great potential, and it could address the existing treatment gap for RET-fusion NSCLC and other RET-altered tumors in this country. I am pleased that through our dedicated efforts, we have successfully carried out the dosing of the first patient in China as a part of the ongoing, global registrational study."

"Precision medicines such as BLU-667 may be highly effective in treating genomically defined cancers and bring significant clinical benefit to patients. The global ARROW study has thus far produced promising clinical data. I am confident that with CStone’s effective execution, we can efficiently accelerate this clinical trial in China so that Chinese patients with RET-altered tumors can access this therapy as soon as possible," noted Dr. Jason Yang, CStone’s Chief Medical Officer.

[1]. Chen W, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-32.

[2]. Priya SR, et al. Targeted Therapy for Medullary Thyroid Cancer: A Review. Front. Oncol. 7:238.

[3]. Justin F. Gainor, et al. Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC). 2019 ASCO (Free ASCO Whitepaper) Abstract 9008.

[4]. Matthew H. Taylor, et al. Activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients with advanced RET-altered thyroid cancers. 2019 ASCO (Free ASCO Whitepaper) Abstract 6018.

About BLU-667

BLU-667 is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. Blueprint Medicines is developing BLU-667 for the treatment of patients with RET-altered NSCLC, MTC and other solid tumors. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation to BLU-667 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.

BLU-667 was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. In preclinical studies, BLU-667 consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, BLU-667 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, BLU-667 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.

On August 12, 2019 Apollo Endosurgery, Inc. ("Apollo") (Nasdaq:APEN), a global leader in less invasive medical devices for gastrointestinal and bariatric procedures, reported that it has closed its previously announced private placement of $20 million of unsecured convertible debentures to accredited and institutional investors (Press release, Lpath, AUG 12, 2019, View Source [SID1234538836]).

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Interest on the debentures is payable semi-annually in common stock, or in kind in certain situations, at a rate per annum of 6.0%. At any time prior to maturity, the debentures are convertible into shares of Apollo’s common stock at a conversion price of $3.25, subject to certain customary adjustments. Upon the satisfaction of price and other conditions, Apollo has the right to force the conversion of the debentures. The debentures are unsecured and rank junior in right of payment to Apollo’s existing senior indebtedness. The outstanding principal and accrued interest on the debentures is due on the five-year anniversary of the issuance date. Apollo intends to use the proceeds from the sale of debentures for working capital and general corporate purposes.

Craig-Hallum Capital Group acted as the exclusive placement agent in connection with this transaction.

The securities sold in the private placement have not been registered under the Securities Act of 1933, as amended, or state securities laws and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission (SEC) or an applicable exemption from such registration requirements. Apollo has agreed to file a registration statement with the SEC registering the resale of the shares of common stock underlying the convertible debentures.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful.