On June 15, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment; TecDAX; Nasdaq: MOR) reported the presentation of clinical data from the exploratory phase 2 COSMOS trial (Press release, MorphoSys, JUN 15, 2018, View Source [SID1234527338]). The trial evaluates MorphoSys’s proprietary hemato-oncological drug candidate MOR208 in combination with the cancer drug idelalisib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), who progressed on or were intolerant to ibrutinib therapy. Data will be presented in a poster presentation on June 15, 2018, at the 23rd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Stockholm/Sweden. MOR208 is an investigational Fc-enhanced humanized monoclonal antibody directed against CD19 in clinical development for the treatment of B cell malignancies.

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"Patients with CLL after failure of ibrutinib therapy are in need of more therapeutic options. We are encouraged by the initial and, for the most part, still ongoing responses observed in this heavily pretreated patient population in our exploratory trial with MOR208 plus idelalisib," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "Overall, this shows the potential medical application of MOR208 in additional B cell malignancies. The data shows that MOR208 may be combined with other cancer drugs used in hematological malignancies, including PI3K inhibitors. We look forward to the upcoming results from the second cohort of MOR208 plus venetoclax of our ongoing COSMOS study which we expect later this year."

COSMOS is a phase 2, two-cohort, open-label, multicenter study evaluating the preliminary safety and efficacy of MOR208 combined with idelalisib (cohort A) or venetoclax (cohort B) in patients with r/r CLL/SLL previously treated with Bruton’s Tyrosine Kinase inhibitor (BTKi) ibrutinib.

Data presented at EHA (Free EHA Whitepaper) 2018 comprise preliminary safety and efficacy data on all 11 patients enrolled into cohort A (cut-off date: January 29, 2018). Patients enrolled had received a median of five prior treatment lines (range: 2-9 prior lines). Nine out of the eleven patients enrolled (82%) had discontinued prior ibrutinib treatment due to progressive disease and two patients (18%) due to toxicity.

The most common treatment-emerging adverse events (TEAEs) of grade 3 or higher were hematologic, with neutropenia observed for four patients (36%) and anemia for three patients (27%) being the most common reported events. Ten treatment-emergent serious adverse events (SAEs) were reported in five patients (45%) none of them being fatal. All except one of the six treatment-related SAEs reported for three patients (27%) were suspected to idelalisib.

According to the preliminary efficacy analysis conducted by the investigators, overall response rate (ORR) was 82%, including one complete response (CR, 9%) confirmed by bone marrow biopsy and eight partial responses (PR, 73%). In addition, two patients (18%) showed stable disease. The median observation time was 4.2 months. At the time of data-cut off, six patients continued treatment. One patient with a very good partial response according to response criteria was taken off the study to receive stem cell transplantation. Two previously responding patients had to discontinue the study due to progressive disease. Two patients (one PR, one stable disease SD) discontinued due to adverse events.

Details about the poster presentation on MOR208 at EHA (Free EHA Whitepaper) 2018:

Abstract Code: PF350

Two-cohort, phase II study in R/R CLL (COSMOS): First preliminary safety and efficacy results of MOR208 treatment in combination with idelalisib in patients who discontinued prior ibrutinib therapy

The poster will be presented during the session "Chronic lymphocytic leukemia and related disorders – Clinical" on Friday, June 15, 2018 5:30-7:00 pm CEST (11:30am-1:00pm EDT), in the poster area at the Stockholmsmässan in Stockholm.

In addition, the corresponding abstract will be on display on the E-poster screens at the conference from Friday, June 15, 2018, 9:30 am CEST (3:30 am EDT) to Sunday, June 17, 2018, 1:00 pm CEST (7:00 am EDT).

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

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) is investigating the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the FDA granted Breakthrough Therapy Designation for MOR208 plus lenalidomide in this patient population. The pivotal phase 2/3 B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. In addition, MOR208 is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.

On June 15, 2018 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the presentation of an integrated analysis of long term safety data of umbralisib (TGR-1202), the Company’s PI3K delta inhibitor, either dosed as a single agent and in combination, in patients with relapsed or refractory lymphoid malignancies, as well as the first preclinical data presentation of TG-1701, the Company’s orally available and covalently-bound BTK inhibitor (Press release, TG Therapeutics, JUN 15, 2018, View Source [SID1234527350]). Data from these trials are being presented today during the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are extremely pleased to present updated data from our integrated safety analyses of umbralisib. There is a generally held belief that severe toxicities are more common following 6 months of exposure on a PI3K delta inhibitor. While this has held true for first generation delta inhibitors, we are pleased to present data from 177 patients on daily umbralisib for more than 6 months, ranging upwards of 5+ years, and believe the long-term follow-up data demonstrates that umbralisib has a differentiated safety profile, uniquely distinct from prior generation PI3K delta inhibitors." Mr. Weiss continued, "The differentiated safety profile of umbralisib is critical as we think about potential triple and quad combination strategies, especially in combination with our novel, proprietary BTK inhibitor, TG-1701, for which we also presented some exciting pre-clinical data. The kinase profile of TG-1701 looks quite competitive with the most specific BTK inhibitors and more selective than ibrutinib. We look forward to seeing more data on TG-1701 and expect to open a TG sponsored Phase 1/2 trial later this year."

Highlights from today’s presentations include the following:

Poster Presentation: Long term integrated safety analysis of umbralisib (TGR-1202), a PI3K delta/CK1-epsilon inhibitor with a differentiated safety profile in patients with relapsed/refractory lymphoid malignancies

This presentation builds on a prior integrated analysis of 347 patients with relapsed or refractory lymphoid malignancies presented last year. The presentation includes data that were pooled from 4 completed or ongoing Phase 1 or 2 studies containing umbralisib, focusing on 177 patients who have been on daily umbralisib for a minimum of 6 months. Patients were heavily pretreated, with 45% of patients having seen 3 or more prior lines of therapy.

Highlights from this poster include:

● Umbralisib continues to exhibit a differentiated safety profile compared to prior generation PI3K delta inhibitors

● 177 patients have been treated with daily umbralisib for 6+ months, with a median duration of exposure of 1.3 years, and 33% patients on drug 2+ years and the longest patients on daily umbralisib for over 5 years

o Serious adverse events occurring in >1% of patients were limited to pneumonia (3%), diarrhea (2%), and cellulitis (2%)

o Only 2% of patients discontinued as a result of diarrhea/colitis after being on umbralisib for more than 6 months
oDiscontinuations due to other adverse events (AEs) of interest for prior generation PI3K inhibitors were also rare

Poster Presentation: TG-1701 is a novel, orally available, and covalently-bound BTK inhibitor

● TG-1701, a novel, specific and covalent BTK inhibitor, is more selective than ibrutinib toward a set of kinases

● BTK occupancy assays in vitro and in vivo suggest that 100% occupancy can be reached using low doses of TG-1701 in human dose escalation clinical trial

● In pre-clinical experiments, TG-1701 inhibited the phosphorylation of BTK and other kinases downstream of the BCR pathway.

● In cellular and animal models of b-cell malignancies, TG-1701 demonstrated similar antitumor efficacy to ibrutinib and acalabrutinib

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.