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 Schrödinger reported an expansion of its computational design collaboration with Morphic Therapeutic ("Morphic"), a biotechnology company focused on developing a new class of oral small-molecule integrin-targeted therapeutics that Schrödinger co-founded with Harvard Professor Timothy Springer, Ph.D., and Polaris Partners (Press release, Schrodinger, AUG 13, 2019, View Source [SID1234538650]). The expanded agreement, signed in May 2019, extends the partnership to discover and design therapeutic compounds leveraging Schrödinger’s industry-leading computational platform. Under the terms of the amended agreement, Schrödinger will receive research funding as well as milestone payments and licensing royalties on candidate compounds that emerge from the collaboration.

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Through their partnership, Morphic and Schrödinger have accelerated the discovery and design of potent and selective integrin inhibitors and activators targeting serious chronic diseases, including autoimmune, cardiovascular, and metabolic diseases, fibrosis, and cancer. Schrödinger technology informs Morphic’s integrin technology, or MInT Platform, which leverages Morphic’s unique understanding of integrin structure and biology to develop a broad pipeline of novel product candidates designed to achieve the potency, high selectivity, and pharmaceutical properties required for oral administration.

"This collaboration brings together Morphic’s unparalleled insights into integrins and our proven, computational physics-based approaches to discovering and optimizing compound design. We’re excited to keep building on the momentum of our partnership, and we’ve seen tremendous validation for this approach through Morphic’s continued maturation, including its collaborations with large pharmaceutical companies and its recent initial public offering," said Ramy Farid, Ph.D., Schrödinger’s Chief Executive Officer. "Extending our partnership will allow us to broaden our pipeline as we work together to tackle serious diseases with high unmet need."

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 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported positive top-line data from the INVICTUS pivotal Phase 3 clinical study of ripretinib, a broad-spectrum KIT and PDGFRα inhibitor, in patients with fourth-line and fourth-line plus gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, AUG 13, 2019, View Source [SID1234538651]).

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"There is a dire unmet need for new therapies that can deliver effective disease control for patients with advanced GIST who have failed currently approved treatment options," said Margaret von Mehren, MD, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. "These top-line data from a Phase 3, randomized, placebo-controlled study are highly impressive and suggest that ripretinib’s approach of targeting the broad spectrum of KIT and PDGFRα mutations known to drive GIST can significantly improve progression free survival in the most heavily pretreated patients. Particularly notable is the magnitude of benefit observed for overall survival in this study."

The INVICTUS Phase 3 clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. The INVICTUS study achieved its primary endpoint of improved PFS as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

In the INVICTUS study, ripretinib demonstrated a median PFS of 6.3 months (27.6 weeks) compared to 1.0 month (4.1 weeks) in the placebo arm and significantly reduced the risk of disease progression or death by 85% (HR of 0.15, p<0.0001) compared to placebo.

For the key secondary endpoint of objective response rate (ORR), as determined by blinded independent central radiologic review using modified RECIST version 1.1, ripretinib demonstrated an ORR of 9.4% compared with 0% for placebo (p-value=0.0504), which was not statistically significant. Ripretinib in this study also showed a clinically meaningful improvement over placebo in terms of the secondary endpoint overall survival (OS) (median OS 15.1 months vs. 6.6 months, HR = 0.36, nominal p-value=0.0004). Since statistical significance was not achieved for ORR, the hypothesis testing of OS was not formally performed. According to the pre-specified hierarchical testing procedure of the endpoints, the hypothesis testing of OS cannot be formally conducted unless the test of ORR is statistically significant. The OS data for the placebo arm includes patients taking placebo who, following progression, were crossed-over to ripretinib treatment.

Ripretinib was generally well tolerated and the adverse event results in INVICTUS were consistent with data from previously presented Phase 1 study results. Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurred in 42 (49%) patients on the ripretinib arm compared to 19 (44%) on the placebo arm. Grade 3 or 4 TEAEs >5% of patients in the ripretinib arm were anemia (9%; n=8), abdominal pain (7%; n=6) and hypertension (7%; n=6). Grade 3 or 4 TEAEs >5% of patients in the placebo arm were anemia (14%; n=6). The below table lists TEAEs >15% in the ripretinib arm compared to placebo.

INVICTUS Phase 3 Clinical Study

Treatment Emergent Adverse Event

Placebo

Ripretinib

(N=43)(1)

150mg
Daily

(N=85)(1)

Any event

42 (98

%)

84 (99

%)

Alopecia

2 (5

%)

44 (52

%)

Fatigue

10 (23

%)

36 (42

%)

Nausea

5 (12

%)

33 (39

%)

Abdominal pain

13 (30

%)

31 (36

%)

Constipation

8 (19

%)

29 (34

%)

Myalgia

5 (12

%)

27 (32

%)

Diarrhea

6 (14

%)

24 (28

%)

Decreased appetite

9 (21

%)

23 (27

%)

Palmar-plantar erythrodysaesthesia syndrome

0

18 (21

%)

Vomiting

3 (7

%)

18 (21

%)

Headache

2 (5

%)

16 (19

%)

Weight decreased

5 (12

%)

16 (19

%)

Arthralgia

2 (5

%)

15 (18

%)

Blood bilirubin increased

0

14 (16

%)

Oedema peripheral

3 (7

%)

14 (16

%)

Muscle spasms

2 (5

%)

13 (15

%)

Notes to table: (1) Safety population includes 128 patients. One patient was randomized to placebo but did not receive study drug.

"Today’s announcement represents a significant milestone in our mission to deliver important new medicines for the treatment of cancer," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "On behalf of the entire Deciphera team, I would like to thank the patients, their caregivers and the healthcare professionals who participated in the INVICTUS study. The data from INVICTUS reinforce our belief that ripretinib has the potential to transform the treatment of GIST, and our focus now turns to working closely with the FDA as they evaluate ripretinib for those patients with GIST who, having failed all currently approved therapies, are in desperate need of a treatment option."

Based on the positive INVICTUS data, the Company expects to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.

Additional results from the INVICTUS Phase 3 clinical study are expected to be presented at an upcoming medical meeting.

Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss the results of the INVICTUS Phase 3 clinical study today, August 13, 2019 at 8:00 AM ET. To access the live call by phone please dial 866-930-5479 (domestic) or 409-216-0603 (international); the conference ID is 8859018. A live audio webcast of the event and accompanying slides may also be accessed through the "Investors" section of Deciphera’s website at www.deciphera.com. A replay of the webcast will be available for 30 days following the event.

About the INVICTUS Phase 3 Study

The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. This study was designed to provide evidence of clinical benefit in fourth-line and fourth-line plus patients with GIST that would be required to secure a regulatory approval. Patients were randomized 2:1 to either 150 mg of ripretinib or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR), Time to Tumor Progression (TTP) and Overall Survival (OS). See www.clinicaltrials.gov for further information (NCT03353753).

About GIST

Gastrointestinal stromal tumor (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in European and other countries. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 75% to 80% of cases, or in PDGFRα kinase, representing approximately 5% to 10% of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.

About Ripretinib

Ripretinib is an investigational KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and other cancers. Ripretinib was specifically designed to improve the treatment of patients with GIST by inhibiting a broad spectrum of mutations in KIT and PDGFRα. Ripretinib is a KIT and PDGFRα inhibitor that inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (Mainland China, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.

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.