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Faslodex (fulvestrant) receives positive CHMP opinion for use in 1st-line hormone receptor-positive advanced breast cancer

On June 23, 2017 AstraZeneca reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending the marketing authorisation of Faslodex (fulvestrant) for the treatment of hormone receptor-positive (HR+), locally-advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-oestrogen therapy, or disease progression on anti-oestrogen therapy (Press release, AstraZeneca, JUN 23, 2017, View Source [SID1234519656]).

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The CHMP recommendation is based on pivotal data from the Phase III FALCON trial, where Faslodex 500mg demonstrated superiority over anastrozole 1mg in the treatment of locally-advanced or metastatic breast cancer in post-menopausal women who had not received prior hormonal-based medicine for HR+ breast cancer.

The FALCON data show that the delay in disease worsening or death (median progression-free survival, PFS) was 2.8 months longer with Faslodex than anastrozole. The median PFS was 16.6 months in the Faslodex arm compared with 13.8 months in the anastrozole arm. Aromatase inhibitors such as anastrozole are the current standard of care for the 1st-line treatment for postmenopausal women with HR+ advanced breast cancer.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "Faslodex has long been an effective medicine for women with advanced breast cancer in later lines of treatment and we are pleased that the CHMP has recognised its potential as a first-line option. Faslodex is also being tested in combination with over 19 different medicines, which is testament to its well-established safety and efficacy profile with over 15 years of patient evidence since its first launch in 2002."

The safety and tolerability profile was in line with current experience with Faslodex and anastrozole. The most-commonly reported adverse events (AEs) in the Faslodex and anastrozole arms were arthralgia (16.7% vs. 10.3%), hot flush (11.4% vs. 10.3%) and nausea (10.5% vs. 10.3%).

Faslodex is the only hormone medicine for advanced breast cancer that slows tumour growth by binding to and degrading the oestrogen receptor – a key driver of breast cancer progression in some women. It is widely approved for the treatment of HR+ advanced breast cancer in postmenopausal women with disease progression following anti-oestrogen medicine.

The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union (EU). The final decision will be applicable to all 28 EU member countries plus Iceland, Norway and Liechtenstein.

NOTES TO EDITORS

About FALCON

The FALCON (Fulvestrant and AnastrozoLe COmpared in hormonal therapy-Naïve advanced breast cancer) trial is a Phase III, randomised, double-blind, multicentre trial comparing the antitumour effects and tolerability profile of a 500mg dose of Faslodex plus placebo with a 1mg dose of anastrozole plus placebo, in postmenopausal women with HR+, locally-advanced or metastatic breast cancer who have not been treated previously with any hormonal medicine.

The FALCON trial was designed on the basis of positive results from the Phase II FIRST trial, which demonstrated a median overall survival nearly six months longer with Faslodex compared to anastrozole.

About Advanced Breast Cancer

Advanced/metastatic breast cancer refers to Stage III and IV breast cancer. Stage III disease may also be referred to as locally-advanced breast cancer, while metastatic disease is the most-advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumour site to other organs of the body outside the breast. Since there is no cure for the disease, the goal of current treatment is to delay disease worsening or death.

About Faslodex

Faslodex (fulvestrant) is indicated for the treatment of postmenopausal women with oestrogen receptor-positive (ER+), locally-advanced or metastatic breast cancer with disease relapse on or after adjuvant anti-oestrogen treatment, or disease progression on treatment with an antioestrogen.

In the US, Faslodex is also approved, in combination with palbociclib, for the treatment of women with HR+, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the oestrogen receptor – a key driver of disease progression.

About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

ArQule Presents Preclinical Data for BTK Inhibitor, ARQ 531, at the 22nd Annual Congress of the European Hematology Association (EHA)

On June 23, 2017 ArQule, Inc. (Nasdaq: ARQL) reported that preclinical data for ARQ 531 in diffuse large B-cell lymphoma (DLBCL) in vitro and in vivo tumor models was presented at EHA (Free EHA Whitepaper) Congress in Madrid, Spain (Press release, ArQule, JUN 23, 2017, View Source [SID1234519655]). ARQ 531 is an investigational, orally bioavailable, potent and reversible inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK).

The presentation titled "ARQ 531, A Reversible BTK Inhibitor, Demonstrates Potent Anti-Tumor Activity in ABC-DLBCL and GCB-DLBCL" can be viewed at View Source

ARQ 531 Poster Presentation Highlights

Preclinical data suggests ARQ 531 has the potential for broad clinical utility in a wide range of hematological malignancies and lymphomas.
The signaling pathways evaluated show a distinct kinase inhibition profile that could be advantageous in treating lymphomas.
ARQ 531, unlike other BTK inhibitors, has activity in both ABC-DLBCL and GCB-DLBCL preclinical models.
A phase 1 trial with ARQ 531 in patients with B-cell malignancies refractory to other therapeutic options, including ibrutinib, is planned to commence by the third quarter of 2017.
"This data further strengthens a very comprehensive preclinical package for ARQ 531," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "While targeting ibrutinib resistant patients will be an initial, fast-to-market strategy for the clinical development of ARQ 531, the data presented at EHA (Free EHA Whitepaper) clearly demonstrate the potential clinical utility of the drug beyond ibrutinib refractory cancers."

B-cell malignancies, like chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia, DLBCL and mantle cell lymphoma are driven by BTK. The only approved BTK inhibitor, ibrutinib, is irreversible and makes a covalent bond with the C481 residue of the targeted protein. Although ibrutinib has demonstrated excellent responses in patients with elevated B-cell receptor signaling, clinical resistance has been observed, and the BTK C481S mutation is emerging as a predominant mechanism of resistance. As a reversible inhibitor, ARQ 531 does not require interaction with the C481 residue, a binding site essential for irreversible ibrutinib binding to BTK, thus positioning ARQ 531 as a targeted therapy for patients harboring C481S-mutant BTK who have developed resistance to irreversible BTK inhibitors.

About BTK and ARQ 531

ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor. Biochemical and cellular studies have shown that ARQ 531 inhibits both the wild type and C481S-mutant forms of BTK. The C481S mutation is a known emerging resistance mechanism for first generation irreversible BTK inhibitors. In preclinical studies ARQ 531 has demonstrated high oral bioavailability as well as good ADME, pharmacokinetic and metabolic properties. The company plans to initiate a phase 1 trial by the third quarter of 2017. BTK is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers.

Acceleron Provides Updated Results from Phase 2 Studies of Luspatercept in Beta-Thalassemia at the 22nd Congress of the European Hematology Association

On June 23, 2017 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development, and commercialization of innovative therapeutics to treat serious and rare diseases, reported preliminary results from the ongoing Phase 2 study of luspatercept in patients with beta-thalassemia during an oral presentation at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Madrid, Spain (Press release, Acceleron Pharma, JUN 23, 2017, View Source [SID1234519653]). Luspatercept is being developed to treat a range of hematologic diseases including beta-thalassemia, myelodysplastic syndromes (MDS), and myelofibrosis as part of a global collaboration between Acceleron and Celgene.

"With beta-thalassemia patients now remaining on study for over two years, we continue to be highly encouraged by luspatercept’s long-term efficacy results and safety profile," said Habib Dable, President and Chief Executive Officer of Acceleron. "Combined with the rapid completion of enrollment in the BELIEVE Phase 3 trial, the program’s momentum continues to build alongside our enthusiasm to potentially transform the treatment of beta-thalassemia patients globally."

Phase 2 Results

A total of 32 transfusion-dependent beta-thalassemia patients have been treated with therapeutic dose levels of luspatercept in the ongoing study.

69% (22 of 32) achieved a reduction in red blood cell (RBC) transfusion burden of at least 33% in any 12-week treatment interval as compared to baseline.
A 12-week fixed interval analysis was conducted to review RBC transfusion reduction during weeks 13 to 24 and weeks 37 to 48 compared to the baseline 12-week period pre-treatment in order to evaluate durability of response. The ongoing BELIEVE Phase 3 trial will use this 12-week fixed interval analysis for evaluating the proportion of patients achieving at least a 33% reduction in RBC transfusion burden.

50% (12 of 24 patients with 6-20 units RBC / 24 weeks estimated pre-treatment) achieved a reduction in RBC transfusion burden of at least 33% in the fixed 12-week interval from weeks 13 to 24 as compared to baseline.
46% (11 of 24 patients with 6-20 units RBC / 24 weeks estimated pre-treatment) achieved a reduction in RBC transfusion burden of at least 33% in the fixed 12-week interval from weeks 37 to 48 as compared to baseline.
A total of 31 non-transfusion-dependent beta-thalassemia patients have been treated with therapeutic dose levels of luspatercept in the ongoing study.

71% (22 of 31) achieved a clinically meaningful increase in hemoglobin of at least 1.0 g/dL compared to baseline (mean increase over 12 weeks).
There are patients who remain on luspatercept with clinically meaningful increases in hemoglobin and reductions in RBC transfusion burden for up to 24 months.

Phase 2 Safety Summary

A total of 64 beta-thalassemia patients have been treated with luspatercept in the ongoing Phase 2 studies (all dose levels).

The majority of adverse events (AEs) were Grade 1 or 2. The most common related AEs (occurring in ≥ 10% of patients) were bone pain, headache, myalgia, arthralgia, musculoskeletal pain, asthenia, injection site pain, and back pain.
Grade 3 AEs probably related to study drug were bone pain (n=3), asthenia (n=2) and headache (n=1).
There were no serious AEs related to study drug.
"Beta-thalassemia remains an area of critical medical need for many patients around the world," said Michael Pehl, President, Hematology/Oncology for Celgene. "These longer-term results continue to illustrate the potential for luspatercept to affect transfusion dependence and hemoglobin levels, making a meaningful impact for patients with this serious blood disease."

Luspatercept is an investigational product that is not approved for use in any country.

The BELIEVE trial, a global Phase 3 study of luspatercept in transfusion-dependent beta-thalassemia patients, is fully enrolled and top-line results are expected in mid-2018.

The EHA (Free EHA Whitepaper) beta-thalassemia presentation is available under the Science page of the Company’s website at www.acceleronpharma.com/.

About the Phase 2 Study

Data from two open-label Phase 2 studies were presented at the conference: the base study in which patients received treatment with luspatercept for three months and the ongoing long-term safety extension study in which patients may receive treatment with luspatercept for up to an additional five years. In both the three-month base study and the long-term extension study, red blood cell (RBC) transfusion-dependent patients (≥ 4 units RBC / 8 weeks) and non-transfusion-dependent patients ( < 4 units RBC / 8 weeks) were enrolled and treated with open-label luspatercept, dosed subcutaneously once every three weeks.

The primary outcome measure of the three-month base study was the proportion of patients who have an erythroid response, defined as 1) a hemoglobin increase of ≥ 1.5 g/dL from baseline for ≥ 14 days (in the absence of RBC transfusions) in non-transfusion dependent patients, or 2) ≥ 20% reduction in RBC transfusion burden compared to pretreatment in transfusion-dependent patients. The primary outcome for the long-term extension study is to evaluate the long-term safety and tolerability of luspatercept.

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the transforming growth factor-beta superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoiesis stimulating agents (ESAs), which stimulate the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials are underway to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the "MEDALIST" study) and in patients with beta-thalassemia (the "BELIEVE" study). For more information, please visit www.clinicaltrials.gov.

AbbVie Announces Pivotal Phase 2 Trial Evaluating VENCLYXTO™ (venetoclax) in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) with 17p Deletion to be Presented at 22nd European Hematology Association (EHA) Annual Congress

On June 23, 2017 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported the presentation of results from the pivotal Phase 2 study of VENCLYXTO (venetoclax), a first-in-class oral B-cell lymphoma-2 (BCL-2) inhibitor (Press release, AbbVie, JUN 23, 2017, View Source [SID1234519652]). VENCLYXTO monotherapy responses in 158 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and 17p deletion showed that 77 percent (95% confidence interval [CI]: 69.9, 83.5) achieved an overall response rate (ORR = complete remission [CR] + complete remission with incomplete marrow recovery [Cri] + partial remission [PR] + nodular partial remission [nPR]) (primary endpoint),1 18 percent achieved a complete remission (CR +CRi) (secondary endpoint), 53 percent achieved a partial remission (PR), 6 percent achieved an nPR,3 and 27 percent achieved blood minimal residual disease (MRD) negativity, as measured by flow cytometry (exploratory endpoint).1 These results, which were based on an investigator assessment, will be presented in an oral session on Sunday, June 25, at the 22nd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Madrid.

VENCLYXTO monotherapy was granted conditional marketing authorization in the EU for the treatment of CLL in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.3 VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

"These response rates associated with venetoclax treatment in patients with CLL and 17p deletion who relapsed or were refractory to prior treatments were evaluated in one of the two pivotal studies that were included in the EU summary of product characteristics for VENCLYXTO for use in this patient population," said Prof. Dr. Stephan Stilgenbauer of the Department of Internal Medicine at Ulm University in Germany, who will present the study results at the EHA (Free EHA Whitepaper) Annual Congress. "In addition, we are encouraged by the results of the secondary and exploratory endpoints included in this Phase 2 trial."

Design and Results of Pivotal Phase 2 Study Presented at EHA (Free EHA Whitepaper) Congress
In the pivotal Phase 2 study, patients with relapsed/refractory CLL harboring 17p deletion received VENCLYXTO 400 mg daily following a four to five-week dose titration phase until they experienced progressive disease or discontinued due to other reasons.1 Assessment of minimal residual disease (MRD) in peripheral blood was performed with the first clinical assessment of complete remission (CR) or partial remission (PR) with nodes less than 2 cm and then every 12 weeks until MRD negativity.1 This means fewer than one CLL cell in 10,000 leukocytes (white blood cells) could be detected.4 A total of 158 study participants had received a median of two prior therapies, and 11 percent had previously received a B-cell receptor signaling inhibitor.1 The median age of study participants was 67 years, and the median duration of VENCLYXTO therapy was 16.7 months (range: 0-34.4).1

An initial analysis of results from 107 patients by an independent review committee showed that VENCLYXTO resulted in an overall response rate (ORR = CR + CRi + PR +nPR) of 79 percent (95% confidence interval [CI]: 70.5, 86.6), a CR +CRi rate of 7 percent, a PR rate of 69 percent, and an nPR rate of 3 percent.3 Subsequently, 51 additional patients were enrolled in a safety expansion cohort.1 Results of the full study cohort of 158 patients showed the investigator-assessed ORR was 77 percent (95% CI: 69.9, 83.5),1 the CR +CRi rate was 18 percent, the PR rate was 53 percent, and the nPR rate was 6 percent.3 Among 18 patients who had received prior BCR inhibitor treatment, the ORR was 61 percent and the CR rate was 11 percent.1 Among the full trial cohort of 158 patients, 27 percent demonstrated MRD negativity (exploratory endpoint) in peripheral blood by flow cytometry.1 A total of 101 patients were evaluable for blood MRD by flow cytometry.1 Progression-free survival (PFS) and overall survival (OS) (secondary endpoints) over 24 months were estimated to be 52 percent and 72 percent, respectively.1

In the study, the most commonly reported adverse events were neutropenia (42 percent), nausea (37 percent), diarrhea (37 percent), anemia (24 percent) and fatigue (22 percent).1 The most common grade 3-4 adverse events were neutropenia (39 percent), thrombocytopenia (15 percent) and anemia (14 percent). Infection rate (77 percent all grades, 22 percent grade 3-4) and spectrum were consistent with the underlying disease.1 The rate of laboratory tumor lysis syndrome (TLS) was 5 percent, with no cases of clinical TLS.1

Phase 1b Venetoclax Data Presented at EHA (Free EHA Whitepaper) Congress
Results from an ongoing Phase 1b investigational study of venetoclax were also presented at the EHA (Free EHA Whitepaper) Congress. This open-label, multicenter study is evaluating the safety and tolerability of venetoclax in combination with rituximab in patients with relapsed CLL/small lymphocytic leukemia (SLL).5 The primary objectives of this study are to assess the safety profile, determine the maximum tolerated dose, and establish the recommended Phase 2 dose of venetoclax when administered in combination with rituximab.5

This analysis evaluated responses in 49 patients with previously-treated CLL/SLL who were treated with venetoclax and rituximab therapy.2 Patients who achieved CR or MRD negativity could stop therapy and remain on the study. Patients who manifested progressive disease (per iWCLL criteria) while off therapy could re-initiate venetoclax and subsequent rituximab therapy. A total of 21 patients discontinued the study.2 A total of 12 had progressive disease while on therapy (five with Richter’s transformation and seven with CLL progression).2 The other nine patients either withdrew consent (five), failed to report for follow-up evaluations (one), discontinued due to adverse events related to venetoclax (one with tumor lysis syndrome and one with worsening peripheral neuropathy) or discontinued due to adverse events considered not related to therapy (one).2 A total of 16 patients stopped venetoclax per protocol.2

In the Phase 1b study, the most commonly reported adverse events were upper respiratory tract infection, neutropenia and mild GI issues. Grade 3-4 adverse events were reported for 37 patients (76 percent); the most common were neutropenia (53 percent), thrombocytopenia (16 percent) and anemia (14 percent).2

As of April 5, 2017, the ORR was 86 percent. 51 percent of patients had achieved an investigator-assessed CR/CRi, 35 percent had achieved PR/nPR, and 59 percent had achieved MRD negativity.2

"We are encouraged by the early results from this Phase 1b study of continuous venetoclax in patients with relapsed/refractory CLL/SLL and in those who received venetoclax in combination with rituximab," said Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie. "We remain committed to developing and delivering therapies that address unmet needs in certain patients with CLL."

About VENCLYXTO (venetoclax)
VENCLYXTO (venetoclax), an oral B-cell lymphoma-2 (BCL-2) inhibitor, is indicated for the treatment of chronic lymphocytic leukaemia (CLL) in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.3 It is also being evaluated for the treatment of patients with various blood cancer types.3,6,7,8,9 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.3 VENCLYXTO, which is given once-daily, is designed to selectively inhibit the function of the BCL-2 protein.3

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL and frontline CLL, along with studies in several other cancers.

Venetoclax is currently approved in several countries in Europe, as well as in Argentina, Australia, Mexico, Puerto Rico, Israel, USA, and Canada. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.

Important VENCLYXTO (venetoclax) EU Safety Information
Contraindications

Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. Concomitant use of preparations containing St. John’s wort.

Special Warnings & Precautions for Use
Tumour lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumour burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS. Blood chemistries should be monitored and abnormalities managed promptly. More intensive measures (including IV hydration, frequent monitoring and hospitalization) should be employed as overall risk increases.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase. CYP3A4 inducers may decrease VENCLYXTO plasma concentrations.

Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (>=20%) of any grade were neutropenia/neutrophil count decreased, diarrhoea, nausea, anemia, upper respiratory tract infection, fatigue, hyperphosphatemia, vomiting and constipation.

The most frequently occurring adverse reactions (>=2%) were pneumonia, febrile neutropenia and TLS.

Discontinuations due to adverse reactions occurred in 9.1% of patients and dosage adjustments due to adverse reactions occurred in 11.8% of patients.

Specific Populations
VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment. Advise nursing women to discontinue breastfeeding during treatment.

This is not a complete summary of all safety information. See VENCLYXTO full summary of product characteristics (SmPC) at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

Repare Therapeutics Raises US$68 Million Series A

On June 22, 2017 Repare Therapeutics Inc. reported a US$68 million Series A financing to advance its platform and pipeline of novel medicines that target genetically defined weaknesses of cancers. Founding investor Versant Ventures co-led the round with MPM Capital (Press release, Repare Therapeutics, JUN 22, 2017, View Source [SID1234520721]). They were also joined by other syndicate investors including Fonds de solidarité FTQ, Celgene Switzerland LLC, an affiliate of Celgene Corporation, and BDC Capital’s Healthcare Venture Fund.

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With this financing, Repare emerges from Versant’s Discovery Engines after an 18-month stealth period during which the company advanced its leading CRISPR-enabled synthetic lethality drug discovery platform, identified several promising oncology targets and moved multiple programs into preclinical development. Founders Daniel Durocher, Ph.D., Agnel Sfeir, Ph.D., and Frank Sicheri, Ph.D., and their respective institutions, played instrumental roles in the company’s formation and growth in partnership with Versant.

"Versant’s commitment to and confidence in Repare’s distinct science has enabled the company to build the team, operations and initial programs away from the spotlight," said Repare CEO Lloyd M. Segal. "With the added leadership of MPM and this syndicate, we are financed to achieve our goal of testing our multiple new, precision oncology therapeutics in a clinical setting."

The core concept of synthetic lethality is that while a tumor can tolerate individual defects in its DNA, there exist combinations of defects that lead to the malignancy’s destruction. The recent approvals of several PARP inhibitors provide clear proof-of-principle for the approach of inducing synthetic lethality. Repare and its founders have developed large-scale and novel methods for discovering additional drug targets that, when inhibited, may induce synthetic lethality. New drugs directed at these targets hold promise to improve cancer treatment both as single therapies and in combination with existing drugs and treatments.

In addition to Segal, a Versant Entrepreneur-in-Residence, Repare’s seasoned management team also includes R&D Head Michael Zinda, Ph.D., who built and led AstraZeneca plc’s Oncology iMed Bioscience group in Boston; and VP of Discovery Cameron Black, Ph.D., an accomplished 18-year leader of Merck Frosst’s medicinal chemistry efforts. Repare has a 20-member team based in Montreal and Boston. To further guide this important investment both Jerel Davis, Ph.D., managing director at Versant, and Todd Foley, managing director at MPM Capital, will join Repare’s board of directors.

"The fields of synthetic lethality and DNA repair have a rich, 20-year history and are poised to deliver impactful new cancer treatments," said Davis. "We are impressed by the speed and precision with which Repare, in collaboration with its founders and scientific advisors, generated impressive insights and multiple novel targets."

Repare’s first disclosed program targets DNA-directed DNA polymerase theta (PolQ), a central component of a pathway that repairs double-strand breaks in cancer cells. NYU School of Medicine has licensed to Repare exclusive rights to drug discovery work targeting PolQ, developed by Dr. Sfeir with the support of NYU Office of Therapeutics Alliances (OTA). This unique polymerase is highly expressed in ovarian, breast and a number of other cancers. In parallel, Repare is progressing several additional programs, with an aim to put its first compound in the clinic in 2019.

"We evaluated nearly every opportunity in the synthetic lethality space and have complete conviction that Repare, its founders and its SAB members represent the leaders in the field," said Foley. "MPM is dedicated to investing in and building companies that seek to find cures for cancer and save lives and we look forward to the advancement of Repare’s programs and the development of these meaningful medicines."

Repare’s founders and scientific advisors are leaders in synthetic lethality and tumor repair machinery research. In addition to Dr. Sfeir from the Department of Cell Biology and the Skirball Institute of Biomolecular Medicine at NYU Langone Medical Center and Drs. Durocher and Sicheri from Toronto’s Lunenfeld-Tanenbaum Research Institute, Repare has assembled a world-class scientific advisory board, including:

Samuel Aparicio, Ph.D., chair of the Breast Cancer Program at BC Cancer Agency and professor of pathology and laboratory medicine at UBC, Vancouver.
Jim Carmichael, M.D. FRCP, lead of the Protein Homeostasis Thematic Center of Excellence at Celgene Corporation. He previously was U.K. regional director of medical science at AstraZeneca plc following its acquisition of KuDOS, where he was CMO and responsible for clinical development of olaparib.
Ronny Drapkin, M.D., Ph.D., director of the Penn Ovarian Cancer Research Center and director of gynecologic cancer research at the Basser Center for BRCA at the University of Pennsylvania.
Laurie Glimcher, M.D., president and CEO of the Dana-Farber Cancer Institute, Richard and Susan Smith Professor of Medicine at Harvard Medical School.
Mark Pegram, M.D., director of the breast cancer oncology program at Stanford Women’s Cancer Center and co-director of Stanford’s molecular therapeutics program.
Richard Wood, Ph.D. FRS, Grady F. Saunders Distinguished Professor in Molecular Biology at the University of Texas MD Anderson Cancer Center.

About Repare

Repare is developing new, precision oncology drugs for patients that target specific vulnerabilities of tumor cells. Its approach integrates insights from several fields of cell biology including DNA repair and synthetic lethality. Repare’s platform combines a proprietary, high-throughput, CRISPR-enabled gene editing target discovery method with high-resolution protein crystallography, computational biology and clinical informatics. The company is backed by leading global healthcare investors including founding investor Versant Ventures and MPM Capital. For additional information, please visit www.reparerx.com.

About Versant

Versant Ventures is a leading healthcare investment firm committed to helping exceptional entrepreneurs build the next generation of great healthcare companies. The firm invests across the healthcare sector and at all stages of company development, with an emphasis on the discovery and development of novel therapeutics. With $2.3 billion under management and offices in North America and Europe, Versant has built a team with deep investment, operating, and scientific expertise that enables a hands-on approach to company building. Since the firm’s founding in 1999, more than 65 Versant companies have achieved successful acquisitions or IPOs. For more information, please visit www.versantventures.com.

About MPM Capital

MPM Capital is an early‐stage life sciences venture firm founding and investing in companies that seek to cure major diseases by translating scientific innovations into positive clinical outcomes. MPM’s portfolio of companies aims to revolutionize the face of medicine across multiple areas including cancer, neuroscience, metabolic disorders, and regenerative medicine. With its experienced and dedicated team of operating executives and medical and scientific advisory board, MPM is powering novel medical breakthroughs that transform patients’ lives. MPM has more than $2.6 billion dollars in assets under management and is currently investing from two funds ─ the BV2014 and UBS Oncology Impact Fund. For further information, please visit www.mpmcapital.com.

About the Fonds de solidarité FTQ

The Fonds de solidarité FTQ is a development capital fund that channels the savings of Quebecers into investments. As at November 30, 2016, the organization had $12.2 billion in net assets, and through its current portfolio of investments has helped create and protect over 187,000 jobs. The Fonds is a partner in more than 2,600 companies and has nearly 618,000 shareholder-savers. fondsftq.com.

About BDC Capital

With more than $2 billion under management, BDC Capital is the investment arm of BDC, serving as a strategic partner to Canada’s most innovative and high potential firms. It offers a range of equity, venture capital and flexible growth and transition capital solutions to help Canadian entrepreneurs scale their businesses into global champions. To find out more, visit bdc.ca/capital.