On December 6, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; Nasdaq: MOR) reported its data from the ongoing single-arm phase 2 clinical trial known as L-MIND in an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2018 in San Diego, USA (Press release, MorphoSys, DEC 6, 2018, View Source [SID1234531937]). L-MIND is designed to investigate the antibody MOR208 in combination with lenalidomide in patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). MOR208 is an investigational humanized Fc-enhanced monoclonal antibody directed against CD19 and is currently in clinical development in blood cancer indications.

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The L-MIND study enrolled patients with r/r DLBCL, who are ineligible for HDC and ASCT, after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy, such as rituximab. The updated interim data reported today (cut-off date June 5, 2018) included all 81 patients enrolled in the L-MIND trial, with a median observation time of 12 months. Efficacy results in this update are based on assessment by the investigators for all 81 patients. Patients enrolled had a median age of 72 years and had received a median of two prior treatment lines.

The data showed a response in 47 out of 81 patients (overall response rate, or ORR, 58%), with complete responses (CR) in 27 (33%) and partial responses (PR) in 20 (25%) patients. The median progression-free survival (mPFS) was 16.2 months (95% confidence interval (CI) 6.3 months – not reached). Responses were durable with the median duration of response (DoR) not reached (95% CI: NR – NR) and 70% of responding patients were without progression at 12 months (12-month DoR rate: 70%, Kaplan-Meier estimate). A significant proportion of patients (37/81; 46%) were still on study treatment, with 19 having been treated for over 12 months. Median overall survival (OS) was not reached (95% CI: 18.6 months – NR); the 12-month OS rate was 73% (95% CI: 63% – 85%).

Efficacy parameters, such as response rates and median PFS showed comparable results in most patient subgroups of interest, including low/low-intermediate versus intermediate-high/high IPI score, rituximab refractory versus not refractory and primary refractory versus not refractory, amongst others.

No unexpected toxicities were observed for the treatment combination and no infusion-related reactions (IRRs) were reported for MOR208. The most frequent treatment-emergent adverse events (TEAEs) with a toxicity grading of 3 or higher were neutropenia in 35 (43%), thrombocytopenia in 14 (17%), and anemia in 7 (9%) patients each. Treatment-related serious adverse events (SAEs) occurred in 16 (19.8%) patients, the majority of which were infections or neutropenic fever. 41 (50.6%) patients required dose reduction with lenalidomide, 58 patients (72%) could stay on a daily lenalidomide dose of 20 mg or higher.

The results reported today confirm data from earlier interim analyses reported from this trial in March 2018, when 68 patients had been eligible for investigators’ efficacy assessment at the Dec 12, 2017 cut-off date.

"Patients with relapsed or refractory DLBCL who, after having failed initial therapies, are ineligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT), need more treatment options," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "We are encouraged by our most recent clinical data from the ongoing L-MIND trial. These support our plan to develop MOR208 in combination with lenalidomide, based on our current FDA breakthrough therapy designation, as a potential chemo-free treatment option for this patient population."

Details about the presentation on L-MIND data at ASH (Free ASH Whitepaper) 2018:

Abstract publication number: 227

Session name: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials"

Session date and time: Saturday, December 1, 2018, 4:00pm-5:30pm PST

Presentation time: 5:00pm PST

Room: Marriot Marquis San Diego Marina, Pacific Ballroom 20, San Diego, California.

MorphoSys will hold an investor & analyst event after the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2018 on December 5, 2018, 10:00am EST (3:00pm GMT, 4:00pm CET) in New York. The presentation, a live webcast and a replay of the webcast will be made available at View Source

About DLBCL

Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of malignant lymphoma worldwide and accounts for approximately 30% of all non-Hodgkin lymphomas. Between 30% and 40% of all patients with DLBCL either fail to respond to or show a relapse to initial therapy. Patients who failed frontline therapy and are not eligible to high dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are reported to have a poor outcome and require more therapeutic options.

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 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 involved in 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 U.S. 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 December 6, 2018 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that results from an ongoing Phase II clinical trial of Puma’s drug neratinib are being presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 6, 2018, View Source [SID1234531921]). The presentation entitled, "Neratinib + fulvestrant for HER2-mutant, HR-positive, metastatic breast cancer: Updated results from the phase 2 SUMMIT trial," are being presented at a Spotlight Session by Lillian M. Smyth, M.D., Breast Medicine Service and Early Drug Development Service, Memorial Sloan Kettering Cancer Center, an investigator of the trial.

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Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets. NERLYNX was granted marketing authorization by the European Commission for the extended adjuvant treatment of hormone receptor-positive HER2-positive early stage breast cancer in September 2018.

The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib administered daily to patients who have solid tumors with activating HER2 or HER3 mutations. In the HER2-mutant, HR-positive breast cancer cohort, 47 patients received 240 mg of neratinib daily in combination with fulvestrant at the labeled dose. In this cohort, 43 patients (92%) had HER2-non-amplified disease, and patients had received a median of 3 prior lines of therapy in the metastatic setting (range 0-11 prior regimens) before entering the trial. All patients had been previously treated with an endocrine agent prior to entering the study, including 25 patients (53%) who had received prior fulvestrant. Further, 20 patients (43%) received prior cyclin-dependent kinase 4/6 (CDK4/6)-inhibitor therapy.

The efficacy summary of the breast cohort that received neratinib + fulvestrant is shown in Table 1 below. The interim efficacy results from the trial showed that for the 47 efficacy evaluable patients, 14 patients (30%) experienced an objective response, which included 4 patients with a complete response and 10 patients with partial responses, and 22 patients (47%) experienced clinical benefit (clinical benefit is defined as confirmed complete response or partial response or stable disease for at least 24 weeks). The median duration of response was 9.2 months and the median progression free survival was 5.4 months. Subgroup analysis demonstrated that patients who had received prior fulvestrant or CDK4/6 inhibitor targeted therapy prior to entering the trial also benefited from treatment of neratinib + fulvestrant. Of note, 6 patients (30%) with prior CDK4/6-inhibitor exposure demonstrated confirmed responses, with the duration of responses ranging from 4.5–14.8 months. Four patients were still on treatment at the time of data reporting.

Table 1: HER2-Mutant, HR-Positive Metastatic Breast Cancer
Phase II SUMMIT Trial Efficacy Summary

Neratinib + Fulvestrant
Subgroups
All Patients
(n=47)

Prior Fulvestrant
(n=25)

Prior CDK4/6 Inhibitor-Based
Therapy (n=20)

Efficacy Endpoint a :
Objective response (confirmed)b – n 14 4 6
CR 4 0 1
PR 10 4 5
Objective response rate (95% CI) 30 (17–45) 16 (5–36) 30 (12–54)
Medianc DOR, months (95% CI) 9.2 (5.5–16.6)
DOR for each responder 9.2; 9.3*; 14.8*; 16.6 4.5; 7.3; 9.2*; 9.3*; 11.2*; 14.8*

Clinical benefitd – n 22 9 8
CR or PR 14 4 6
SD 8 5 2
Clinical benefit rate (95% CI) 47 (32–62) 36 (18–58) 40 (19–64)

Medianc PFS (95% CI) time to event, months 5.4 (3.7–9.2) 3.7 (3.5–6.9) 4.1 (1.9–10.9)

Patients with RECIST v1.1 Measurable Disease
Subgroups
Efficacy Endpoint a : All Patients
(n = 39)

Prior Fulvestrant
(n = 21)

Prior CDK4/6 Inhibitor-Based
Therapy (n=15)

Objective response (confirmed)b – n 12 4 5
CR 2 0 0
PR 10 4 5
Objective response rate (95% CI) 31 (17–48) 19 (5–42) 33 (12–62)

Medianc DOR, months (95% CI) 9.0 (4.5–16.6)
DOR for each responder 9.2; 9.3*; 14.8*; 16.6 4.5; 7.3; 9.2*; 9.3*; 14.8*

Clinical benefitd – n 18 8 6
CR or PR 12 4 5
SD 6 4 1
Clinical benefit rate (95% CI) 46 (30–63) 38 (18–62) 40 (16–68)
Medianc PFS (95% CI) time to event, months 5.4 (3.5–10.3) NA NA
a

Response is based on investigator tumor assessments per RECIST v1.1 or modified PERCIST for patients with only PET-evaluable lesions.

Overall objective response (ORR) is defined as either a complete or partial response that is confirmed no less than 4-weeks after the criteria for response are initially met.

Kaplan-Meier analysis

Clinical benefit rate (CBR) is defined as confirmed CR or PR or stable disease (SD) for at least 24 weeks (within +/- 7 day visit window).

Patient still on treatment at time of data cut; DOR, duration of response; PFS, progression free survival; NA, not available

The safety profile observed in neratinib + fulvestrant-treated breast cancer patients in the SUMMIT study was consistent with that observed previously in metastatic patients with HER2 amplified tumors. With anti-diarrheal prophylaxis and management, diarrhea was not a treatment-limiting side effect in SUMMIT. The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 47 patients enrolled in the trial, 11 patients (23%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for those patients was 1.5 days. No patients permanently discontinued neratinib due to diarrhea.

Dr. Lillian Smyth said, "Somatic HER2 mutations represent a distinct class of oncogenic driver mutations that appear to be clinically actionable for metastatic breast cancers. The combination of neratinib plus fulvestrant therapy demonstrates encouraging clinical activity with durable responses in this heavily pretreated metastatic breast cancer patient population with HER2-mutated and hormone receptor-positive disease."

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are very pleased with the updated activity seen with neratinib in combination with fulvestrant in this cohort of patients with HER2-mutated breast cancer. We look forward to the further development of the combination of neratinib and fulvestrant in this patient population."

On December 6, 2018 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported it will host a conference call to discuss the recent discovery of a use of one its molecule for cancer treatment and provide a business update (Press release, Moleculin, DEC 6, 2018, View Source [SID1234531938]). The call will be at 4:30 p.m. ET on Wednesday, December 12, 2018.

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Participants can dial (800) 860-2442 or (412) 858-4600 to access the conference call, or can listen via a live Internet web cast, which is available in the Investor Relations section of the Company’s website at www.moleculin.com. A webcast replay will be available in the Investors section of the Company’s website at www.moleculin.com for 90 days. A teleconference replay will be available at (877) 344-7529 or (412) 317-0088, confirmation code 10126965, through December 19, 2018.

On December 6, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), reported that the United States Patent and Trademark Office has issued US patent 10,144,770, entitled "Chimeric Receptors and Uses Thereof in Immune Therapy." The ‘770 patent covers design and use of the chimeric Antibody-Coupled T-cell Receptor (ACTR) platform technology that enables an engineered immune cell to be targeted via an antibody to attack certain cell types, including cancer cells (Press release, Unum Therapeutics, DEC 6, 2018, View Source [SID1234531923]). An ACTR-expressing T cell offers a number of potential advantages over alternative cell therapy approaches and clinical proof-of-concept for the ACTR technology has been demonstrated in two independent clinical trials sponsored by Unum Therapeutics. ACTR therapeutic programs targeting non-Hodgkin lymphoma, multiple myeloma, and HER2+ advanced cancers are currently in early stages of clinical testing.

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The initial ACTR construct was developed by Dr. Dario Campana, a well-renowned cancer researcher recognized as an inventor of the chimeric antigen receptor that forms the basis for tisagenlecleucel, the world’s first approved CAR-T therapy. Working initially at St. Jude Children’s Research Hospital and later at the National University of Singapore, Dr. Campana and his team were able to demonstrate in mouse studies that ACTR-expressing T cells exhibit potent anti-tumor activity. Researchers at Unum Therapeutics extended upon this work, demonstrating that a wide range of functional ACTR receptors could be constructed using different building blocks derived from various human immune cell receptors.

Under the terms of a 2014 three-way license agreement between Unum Therapeutics, the National University of Singapore, and St. Jude Children’s Research Hospital, Unum Therapeutics controls exclusive, world-wide rights to develop and commercialize ACTR therapies covered by the ‘770 patent. Unum has continued to build a broad patent portfolio encompassing further enhancements to and novel applications of the ACTR technology. In addition to the ‘770 patent covering ACTR in the United States, previously granted patents protect the technology in Europe, Japan, and other important territories. The full text of the ‘770 patent is available from the US Patent and Trademark Office website at View Source;Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=10144770.PN.&OS=PN/10144770&RS=PN/10144770.

On December 6, 2019 Helix BioPharma Corp. (TSX, FSE: "HBP") ("Helix" or the "Company"), an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, reported it has closed a first tranche of a private placement financing for gross proceeds of CAD871,200. The Company expects to complete a second tranche of the private placement financing before the end of December.

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The terms of the placement are for the purchase of units at $1.20 per unit. Each unit is comprised of one common share and one common share purchase warrant. Each common share purchase warrant will entitle the holder to purchase one common share at an exercise price of $1.50 and have an expiry of five years from the date of issuance. Helix intends to use the net proceeds of the private placement for working capital and research and development activities.

ACM Alpha Consulting Management AG provided financial advisory services to Helix in connection with the private placement.