On June 15, 2018 Molecular Partners AG (SIX: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported that the company will present updated preliminary results from the ongoing Phase 2 study of its lead proprietary oncology drug MP0250 at the 23th Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm (Press release, Molecular Partners, JUN 15, 2018, View Source [SID1234527337]).

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The ongoing, open label Phase 2 clinical study[1] is examining the safety and efficacy of MP0250 in combination with bortezomib (Velcade) and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) who have failed at least two lines of standard therapies, including bortezomib and an IMiD. The study is being performed at nine centers in Germany, Poland and Italy.

In the first of two cohorts, patients received MP0250 at 8mg/kg every 3 weeks (corresponding to 66% of the recommended dose) in combination with standard doses of bortezomib and dexamethasone.

All patients had been pretreated with at least two lines of therapy, including an IMiD and bortezomib. 50% of those patients were considered proteasome refractory. At the data cutoff on May 21, 2018, five of eight evaluable patients achieved an objective response (4 patients with PR/partial response; 1 patient with VGPR/very good partial response). Responses were durable, with median time on treatment for responding patients of 22.5 weeks and the longest response still ongoing at 41 weeks.

Main adverse events were consistent with the known side effect profile of VEGF-targeting agents and of Velcade, respectively: thrombocytopenia (4 out of 8 patients), hypertension (3 out of 8 patients) and upper respiratory infection (3 out of 8 patients).

"We are very encouraged by the initial activity and the safety profile of MP0250 in combination with bortezomib and dexamethasone, even at the low dose of MP0250. We have started the treatment of the first two patients with the higher dose of 12 mg/kg which may be even more effective," said Andreas Harstrick, Chief Medical Officer of Molecular Partners.

Patrick Amstutz, CEO of Molecular Partners added: "These results further substantiate our development plans in multiple myeloma as well as the launch of our additional phase 1b/2 study of MP0250 in combination with osimertinib in EGFR-mutated NSCLC."

The ongoing Phase study of MP0250 in multiple myeloma is currently recruiting patients at the higher dose of 12mg/kg q3weeks. Overall, a total of at least 40 patients are planned to be treated. Additional safety and efficacy data are expected by the end of 2018.

An additional phase 1b/2 study will evaluate MP0250 in combination with osimertinib in patients with EGFR-mutated NSCLC pretreated with osimertinib (Tagrisso). The study is conducted in the US and is open for patient enrollment[2].

Full details on the Molecular Partners’ poster presentation today, from 5.30 to 7.00pm CET, at EHA (Free EHA Whitepaper) Stockholm can be found on the conference website. Following its presentation at EHA (Free EHA Whitepaper), the poster will also be available one the Molecular Partners website.

[1] ClinicalTrials.gov identifier NCT03136653

[2] ClinicalTrials.gov identifier NCT03418532

*DARPin is a registered trademark owned by Molecular Partners AG.

Financial Calendar
August 30, 2018 – Publication of 2018 Half-year Results
November 01, 2018 – Q3 2018 Management Statement
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About MP0250
MP0250 is a multi-DARPin candidate targeting simultaneously VEGF and HGF, two prominent escape pathways, and has the potential to reverse resistance that has built to standard of care cancer therapies. Increases in VEGF and HGF are associated with disease progression in multiple myeloma and have been linked to poor prognosis. They are known to be able to stimulate neovascularization, bone destruction, and myeloma proliferation, migration, and adhesion in the bone marrow.

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.
With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in Phase 3, in partnership with Allergan.
Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in Phase 1 clinical development for the treatment of solid tumors and in Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has moved into Phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.

Dr Reddy’s has filed a 20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 20-F, Dr Reddy’s, 2018, JUN 15, 2018, View Source [SID1234527343]).

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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 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