On June 15, 2018 Kitov Pharma Ltd. (NASDAQ:KTOV) (TASE:KTOV), an innovative biopharmaceutical company, reported positive results in a pre-clinical study testing NT219, a first-in-class small molecule targeting IRS1/2 and STAT3, two signal proteins that are part of an anti-cancer drug resistance mechanism (Press release, Kitov Pharmaceuticals , JUN 15, 2018, View Source [SID1234527355]). The study, conducted by Kitov’s majority-owned subsidiary, TyrNovo Ltd., evaluated NT219 in combination with gemcitabine in a patient-derived xenograft (PDX) model of pancreatic cancer and was conducted in accordance with guidance from the U.S. Food and Drug Administration (FDA). The results support the planned submission of the Investigational New Drug (IND) Application for NT219.

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NT219 was tested at three dose levels in combination with gemcitabine vs. gemcitabine alone. A clear dose response effect was observed among treatment arms with statistically significant differences among groups (p-value <= 0.0166). In addition, the study confirmed previous findings that demonstrated the beneficial effect of the combination of NT219 with gemcitabine vs. gemcitabine alone (p-value <0.0001).

Kitov also announced that it has agreed to acquire all of the shares of TyrNovo held by the last remaining unaffiliated shareholder, representing approximately 3.1% of TyrNovo’s issued and outstanding shares, based on an agreed upon TyrNovo company valuation of $10 million. In exchange for the TyrNovo shares and termination of all shareholder and investment agreements with this shareholder, Kitov will issue 2,816,900 new ordinary shares (equivalent to 140,845 American Depositary Shares (ADS)) of Kitov. Following the closing of this transaction, Kitov will hold approximately 97.1% of TyrNovo’s issued and outstanding ordinary shares. The remaining 2.9% of TyrNovo’s shares are held by Dr. Hadas Reuveni, TyrNovo’s founder and chief technology officer.

"These compelling NT219 pre-clinical results represent an important milestone towards the submission of an IND and the initiation of a clinical trial, which we expect will occur in 2019," said Isaac Israel, Kitov’s CEO. "Based on the results generated to date and its profile, we believe NT219 has the potential to be a new treatment option for pancreatic cancer patients. This compelling product candidate previously demonstrated impressive efficacy results in converting non-responding tumors to responders, as well as blocking tumor progression in combination with various oncology drugs, and in a wide range of tumor types. These positive data also further our confidence in the potential of TyrNovo to create significant value for Kitov’s shareholders. As such, we are pleased to have completed the acquisition of substantially all of the remaining minority shares of TyrNovo, and look forward to the continued development of NT219 in oncology."

About TyrNovo

TyrNovo Ltd., a Kitov Pharma (NASDAQ/TASE:KTOV) company, is a developer of novel small molecules in the oncology therapeutic field. TyrNovo is developing NT219, an oncology product designed to be used in combination with other oncology drugs. NT219 is a small molecule dual inhibitor of Insulin Receptor Substrate (IRS1/2) and of Signal Transducer and Activator of Transcription (STAT3), two signal pathways that are involved in the development of cancer drug resistance. In combination with various approved oncology drugs, NT219 has demonstrated potent anti-tumor effects and increased survival in various cancer models, including sarcoma, melanoma, pancreatic, lung, ovarian, head & neck, prostate and colon cancers. Its mechanism of action is through the prevention of acquired resistance in tumors and by regression of resistant tumors. For more information on TyrNovo please visit View Source

On June 15, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; Nasdaq: MOR) reported its updated data from the ongoing phase 1/2a study of the anti-CD38 antibody MOR202 in relapsed/refractory multiple myeloma at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting 2018 in Stockholm (Press release, MorphoSys, JUN 15, 2018, View Source [SID1234527339]). The dose escalation trial comprises three arms: MOR202, MOR202 in combination with the immunomodulatory drug (IMiD) lenalidomide (LEN), and MOR202 in combination with the IMiD pomalidomide (POM), in each case with low-dose dexamethasone (DEX).

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"We are optimistic about the responses seen in patients with multiple myeloma treated with MOR202 plus LEN/DEX and POM/DEX based on matured data as well as about the low proportion of patients experiencing infusion-related reactions," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "There is a medical need for new treatment options in multiple myeloma and we look forward to further maturing data from this ongoing trial."

In total, 56 patients were evaluable for safety and efficacy analysis in the clinically relevant dose cohorts of MOR202 (4 mg/kg, 8 mg/kg, 16 mg/kg) by the time of the data cut-off at December 31, 2017. At data cut-off, 16 patients remained in the study. Of the 56 evaluable patients, 18 had received MOR202 plus DEX, 21 received the combination of MOR202 and POM/DEX and 17 received MOR202 plus LEN/DEX.

MOR202 was given as a two-hour infusion up to the highest dose of 16 mg/kg. Infusion-related reactions (IRRs) occurred in 11% of patients in the clinically relevant dose cohorts of MOR202 and were limited to grade 1 or 2. Further, infusion time could be shortened to 30 minutes in the majority of the 16 patients remaining on study as per the data cut-off date.

The most frequent adverse events of grade 3 or higher were neutropenia, lymphopenia, and leukopenia in 52%, 48%, and 39% of patients, respectively. No unexpected safety signals were observed.

Patients treated with MOR202 in combination with LEN/DEX had a median of two prior treatment lines, 59% being refractory to at least one prior therapy. Median progression-free survival (PFS) was not yet reached. With six of the 17 patients in this cohort still on study at data cut-off, the median follow-up was 16.6 months. An objective response was observed in eleven out of 17 patients (65%), with two complete responses (CR), three very good partial responses (VGPR) and seven partial responses (PR).

Patients receiving MOR202 with POM/DEX, had a median of three prior treatment lines, all being refractory to the last prior therapy. Median PFS was 17.5 months. With ten out of 21 patients in this cohort still on study at data cut-off, the median follow-up was 6.5 months. An objective response was observed in ten out of 21 patients (48%), with two patients achieving a complete response (CR), four patients with a very good partial response (VGPR) and four partial responses (PR).

Patients treated with MOR202 plus DEX had a median of three prior treatment regimens, with 67% being refractory to any prior therapy. Median PFS in this cohort was 8.4 months. All patients had discontinued the study before data cut-off, i.e., follow-up for this cohort is completed. An objective response was observed in five out of 18 patients (28%).

Details of the MOR202 presentation at EHA (Free EHA Whitepaper) 2018

Abstract Code: S848

MOR202 with low-dose dexamethasone (DEX) or pomalidomide/DEX or lenalidomide/DEX in relapsed or refractory multiple myeloma (r/r MM): A phase I/IIa, multicenter, dose-escalation study

The oral presentation will be given during the session "New therapeutic strategies to improve the outcome of relapse/refractory plasma cell disorders" on Saturday, June 16, 2018, from 4:15-4:30pm CEST (10:15-10:30am EDT), in Room A1 at the Stockholmsmässan in Stockholm.

Additional information can be found at www.ehaweb.org, including the abstracts.

On June 15, 2018 Aclaris Therapeutics, Inc. (NASDAQ:ACRS), a dermatologist-led biopharmaceutical company committed to identifying, developing, and commercializing innovative therapies to address significant unmet needs in dermatology and immunology, reported the expansion of its executive leadership team with the appointment of David Gordon, MB ChB, as Chief Medical Officer (Press release, Aclaris Therapeutics, JUN 15, 2018, View Source [SID1234527341]). Dr. Gordon will report to President and Chief Executive Officer, Dr. Neal Walker, and will lead Aclaris’ clinical research and medical affairs functions. Christopher Powala, Chief Regulatory and Development Officer, has added Elaine Morefield, Ph.D to his team as Director, Product Quality. Product Quality was Dr. Morefield’s area of focus for more than eight years at the U.S. Food and Drug Administration (FDA).

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"We are excited to have David join the leadership team at this critical time when we are expanding the number of clinical programs for our pipeline of JAK inhibitors and preparing to initiate a Phase 3 program for common warts," said Dr. Walker. "David has a wealth of experience developing first-in-class treatments and drugs with stand-out clinical profiles," he added.

Prior to joining Aclaris, Dr. Gordon was Senior Vice President and Head of Dermatology Research and Development at GlaxoSmithKline plc (GSK). Over eighteen years at GSK, he led teams responsible for all stages of research from drug discovery through development and post-approval. He served as Clinical Vice President and Medicine Development Leader in the Immuno-Inflammation and Biopharmaceutical groups at GSK. His experience includes successfully developing and obtaining regulatory approval for drugs in a range of therapeutic areas, including NUCALA (mepolizumab)‎ and BENLYSTA (belimumab). His British medical degree (MB ChB) was awarded from Aberdeen University. He is accredited as a specialist in Pharmaceutical Medicine by the Faculty of Pharmaceutical Medicine in London.

"The time I have spent in immuno-inflammation and dermatology has taught me about both the impact of dermatological diseases and how we can apply our knowledge of science to address the needs of these patients," said Dr. Gordon. "I am pleased to be joining Aclaris, a company that is passionate about finding solutions for these patients by developing and commercializing new therapies for dermatologic conditions, including diseases for which no FDA-approved medications exist."

Aclaris also welcomes the addition of Dr. Elaine Morefield. While at the FDA, Dr. Morefield managed the New Drug Application CMC review process and implementation of FDA’s quality by design (QbD) effort. Dr. Morefield’s 30 years of pharmaceutical product development experience also includes positions at Wyeth, Schering-Plough, DSM, and Vertex Pharmaceuticals. Dr. Morefield has had an instrumental role in the development of over one hundred pharmaceutical products.

"I share Dr. Gordon’s enthusiasm for contributing to the efforts of Aclaris to develop new treatments for underserved dermatologic diseases," said Dr. Morefield.

"We are thrilled that Dr. Morefield has joined Aclaris and is contributing her considerable expertise in regulatory strategy and unique insight into FDA," adds Christopher Powala.

On June 15, 2018 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, reported that new interim data from the Phase 1b dose escalation study evaluating AFM13, its lead NK cell engager candidate, at the European Hematology Association (EHA) (Free EHA Whitepaper) 23rd Congress in Stockholm (Press release, Affimed, JUN 15, 2018, View Source [SID1234527342]). Dr. Eva Domingo of the Instituto Catalán de Oncología L’Hospitalet, Barcelona, Spain, presented the poster, titled A Phase 1 Study Investigating the Combination of AFM13 and the Monoclonal Anti-PD-1 Antibody Pembrolizumab in Patients with Relapsed/Refractory Hodgkin Lymphoma after Brentuximab Vedotin Failure: Updated Safety and Efficacy Data. The poster is available on the Affimed website at: View Source

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Assessment of 18 patients treated at the highest AFM13 dose showed best overall response rate (ORR) of 89% (16/18 patients) and complete metabolic response rate (CmR) of 28% (5/18 patients). The ORR and CmR for these 18 patients compare favorably to those of anti-PD-1 monotherapy in similar patient populations.

Responders included three patients who were either primary refractory to or had relapsed during front-line therapy and were refractory to all subsequent lines of therapy. The combination of AFM13 and pembrolizumab was well tolerated, with most adverse events mild to moderate in nature and manageable with standard of care measures.

"The high response rates in this study, in terms of both partial and complete responses, continue to compare favorably to the historical data of anti-PD-1 monotherapy, and would be expected to translate into meaningful progression free and overall survival over time," said Dr. Stephen Ansell, Principal Investigator of the study. "Importantly, these data have shown that AFM13 can be safely administered in combination with Keytruda and has the potential to improve patient outcomes."

A total of 30 patients were recruited into the Phase 1b study with enrollment completed in February 2018. The interim analysis included 24 of the 30 patients (6 from cohorts 1 and 2, and 18 from cohort 3 and the extension cohort) who had undergone at least one post-baseline disease assessment as of the data cut-off date.

"We are very excited about the potential opportunities for AFM13 to benefit patients with CD30-positive malignancies," said Dr. Leila Alland, Affimed’s Chief Medical Officer. "We are planning additional studies of AFM13 in patients with CD30-positive malignancies and are actively seeking guidance from experts on our development plans including potential accelerated approval paths."

Conference Call and Webcast Information

Affimed’s management will host a conference call today, June 15, 2018, at 8:30 a.m. ET. For both "listen-only" participants and those participants who wish to take part in the question-and-answer session, the call can be accessed by dialing +1 929-477-0448 (international numbers are available on Affimed’s homepage) five minutes prior to the start of the call and providing the Conference ID 6246081. A webcast of the conference call can be accessed in the "Events" section on the "Investors & Media" page of the Affimed website at View Source A replay of the webcast will be available on Affimed’s website shortly after the conclusion of the call and will be archived on the Affimed website for 30 days following the call.

About AFM13

AFM13 is a first-in-class tetravalent, bispecific NK cell engager that specifically binds to CD30 on tumor cells and to CD16A on NK cells. AFM13 is being developed in Hodgkin lymphoma (HL) and

in other CD30-positive lymphomas. AFM13 has shown a favorable safety profile and signs of therapeutic efficacy in a monotherapy setting in studies in Hodgkin Lymphoma and CD30+ lymphoma with cutaneous manifestation. In addition, data from a combination study of AFM13 with Merck’s anti-PD1 antibody Keytruda (pembrolizumab) supports proof of principle for the combination of NK cell engagement with checkpoint inhibition. AFM13 has been granted orphan drug designation by the U.S. Food and Drug Administration.

About Affimed’s Phase 1b study of AFM13 in combination with Keytruda (pembrolizumab) (NCT02665650)

Ongoing Phase 1b study to evaluate the safety and tolerability of the combination of the Affimed’s lead product candidate AFM13 with pembrolizumab (Keytruda) as salvage therapy after failure of standard therapies including brentuximab vedotin (BV) in relapsed or refractory (R/R) Hodgkin lymphoma (HL). Patients received escalating doses of AFM13 in combination with pembrolizumab at a flat dose of 200 mg administered every 3 weeks following the classical 3+3 design. Response assessment is performed every 12 weeks by PET/CT according to the Lugano Classification Revised Staging System for malignant lymphoma.

On June 15, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG-806, a highly potent pan-FLT3/pan-BTK inhibitor, exhibits a distinct mechanism of action and greater potency on patient-derived hematologic cancer cells than ibrutinib, a BTK inhibitor approved for the treatment of certain hematologic malignancies (Press release, Aptose Biosciences, JUN 15, 2018, View Source;p=RssLanding&cat=news&id=2354764 [SID1234527344]). The data were presented in a poster on Friday, June 15, at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), taking place June 14-17, 2018 in Stockholm, Sweden.

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CG-806 is an oral small molecule pan-FLT3/pan-BTK inhibitor being developed by Aptose for acute myeloid leukemia (AML) and B-cell malignancies. It is a highly potent, reversible (non-covalent) inhibitor of the wild type and mutant forms of the Bruton’s tyrosine kinase (BTK) enzymes. Ibrutinib, a covalent BTK inhibitor approved for chronic lymphocytic leukemia (CLL) and certain B-cell malignancies, is limited by acquired resistance, as well as refractory disease and tolerance challenges.

The poster, entitled CG’806, A NON-COVALENT PAN-FLT3/PAN-BTK INHIBITOR, EXHIBITS UNIQUE BINDING TO WILD TYPE AND C481S MUTANT BTK AND GREATER POTENCY THAN IBRUTINIB AGAINST MALIGNANT B CELLS, compared CG-806 and ibrutinib with respect to BTK binding mode, kinase inhibition profiles and cytotoxic activity against patient-derived and cultured malignant B-cells. Kinase profiling revealed that CG-806 most potently inhibits kinases from the BTK, FLT3, TRK, and AURK clusters and had similar potency against BTK-WT (IC50 = 8.4 nM) and C481S mutant (IC50 = 2.5 nM), as opposed to ibrutinib that was >60-fold less potent against the C481S mutant. CG-806 did not inhibit TEC, EGFR or ERBB2/4, which are related to ibrutinib’s side effects; CG-806 also demonstrated a favorable safety profile. CG-806 inhibited cell proliferation 2-6,000 times more potently than ibrutinib in 14 tested malignant B-cell lines; it also had greater activity on primary CLL samples than ibrutinib.

"A safe and potent agent that inhibits all forms of BTK and other key rescue pathways (including AKT/PI3K, ERK and NFƙB) is needed for patients intolerant, refractory and resistant to ibrutinib," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "These data strongly support the clinical development of CG-806 to address the limitations and challenges of ibrutinib. CG-806 is being readied for the clinic and we look forward to reporting on its development."

The EHA (Free EHA Whitepaper) poster can be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.

About CG-806

CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors.