On October 22, 2018 SELLAS Life Sciences Group, Inc. (Nasdaq:SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported data from the prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial of the combination of nelipepimut-S (NeuVax, NPS) +/- trastuzumab (Herceptin) targeting HER2 low-expressing breast cancer patient cohorts (Press release, Sellas Life Sciences, OCT 22, 2018, View Source [SID1234530095]). The data were presented in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Meeting, being held in Munich, Germany.

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"These data presented at ESMO (Free ESMO Whitepaper) today highlight the therapeutic potential of NPS for patients with early-stage triple negative breast cancer (TNBC), who currently face limited and ineffective treatment options in the adjuvant setting," said Dr. Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The combination of NPS and trastuzumab demonstrated a clinically meaningful and statistically significant difference in the cohort of patients with TNBC with a 75.2% reduction in risk of relapse or death at 26 months. Importantly, following review of the final data that were also assessed by the independent Data Safety Monitoring Board (DSMB) on October 15, 2018, there was an incremental further improvement of clinical benefit to patients now observed in comparison with the data from the interim analysis completed more than six months ago."

The key data from today’s presentation, based on the final analysis, are shown below, including the summary table and the Kaplan-Meier (K-M) survival curve showing specifically the TNBC cohort:

Safety: Most treatment-emergent adverse events (TEAEs) were of mild or moderate (G1/2) severity (local: 98%; systemic: 93%). The majority of G3 systemic TEAEs were unrelated to NPS. Treatment-related adverse events consisted of manageable local injection site reactions, skin induration, pruritus, and fatigue.

Efficacy:
Outcomes Summary (comparison between the 2-arms of the study, i.e., Active: NPS + TZ, and Control: TZ alone):

Outcome Parameters ITT TNBC cohort No hormone Rx cohort
N (both arms) 275 97 110*
Hazard ratio (HR) 0.62 0.26 0.23
P-value .175 .013 .008
Risk reduction at 24 mo (%) 37 75.2 75.9
24-mo DFS rate (Active) (%) 89.8 92.6 93.2
24-mo DFS rate (Control) (%) 83.8 70.2 71.7
*all patients from the TNBC cohort were included in the No Hormone Rx cohort

Log-rank (K-M) Disease-Free Survival (DFS) over the duration of the study in the TNBC cohort:
SELLAS Life Sciences Group
A chart accompanying this announcement is available at View Source

Notably, the patient demographics and baseline disease characteristics were well balanced between the two arms, both in the intention-to-treat (ITT) and TNBC populations.

Elizabeth A. Mittendorf, M.D., Ph.D., Rob and Karen Hale Distinguished Chair in Surgical Oncology, Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital, Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center, and the Principal Investigator of the Phase 2b study commented: "It is encouraging to see that the final analysis of the NPS +/- trastuzumab Phase 2b trial for the TNBC cohort not only confirms the previously reported positive data, presented in full today, but also provides evidence for a significant clinically positive outcome with the combination. In many early stage TNBC patients, the benefit of initial treatment with neoadjuvant chemotherapy is incomplete, leaving room for improvement, especially in the adjuvant or maintenance setting. To date, targeted therapies have not proven effective for TNBC. Putting HER2 in the crosshairs of an immunotherapeutic combination, in this case NPS plus trastuzumab in triple-negative (HER2 IHC 1+/2+; hormone receptor negative) breast cancer patients, makes sense biologically considering preexisting activated cellular immunity in most patients with these tumors and the pharmacodynamic synergy between these two agents."

Dr. Stergiou further stated, "We look forward to continuing our discussions with U.S. and European regulatory agencies on the most optimal and expeditious development path for NPS in TNBC. To that end, we will be meeting with the FDA in December. We are also engaging in ongoing discussions with potential partners. I would like to thank all patients who participated in this NPS study, and their families and outstanding physicians, as well as our team at SELLAS and our supportive stockholders. As October is breast cancer awareness month, one could not have thought of a better timing to present this data, consistent with our mission to develop potentially life-saving drugs for patients in need."

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

Conference Call

SELLAS will host a conference call on Monday, October 22, 2018 at 8:00 a.m. ET to discuss these data. To participate in the conference call, please dial (866) 416-7995 (domestic) or +1 (409) 217-8225 (international) and refer to conference ID 5571389. A live webcast of the call can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.sellaslifesciences.com.

An archived webcast recording will be available on the SELLAS website beginning approximately two hours after the call.

About ESMO (Free ESMO Whitepaper)

The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) is Europe’s leading non-profit medical oncology organization. ESMO (Free ESMO Whitepaper) is a membership-based society, comprising of 500 expert committee members and 18,000 oncology professionals. ESMO (Free ESMO Whitepaper) organizes a large number of meetings to provide its members and the community with the resources they need and also plays a major role in public policy and European affairs. The ESMO (Free ESMO Whitepaper) 2018 Annual Meeting represents a multi-professional platform for oncology education and exchange, and for immense international visibility for scientific research, and will be held under the tagline "Securing access to optimal cancer care."

On October 22, 2018 Aclaris Therapeutics, Inc. (Nasdaq: ACRS), a dermatologist-led, biopharmaceutical company focused on identifying, developing, and commercializing innovative therapies to address significant unmet patient needs in aesthetic and medical dermatology and immunology, reported the closing of its underwritten public offering of 9,941,750 shares of its common stock at a price to the public of $10.75 per share, which includes the full exercise of the underwriters’ option to purchase 1,296,750 additional shares, for total gross proceeds of approximately $106.9 million, before deducting underwriting discounts and commissions and offering expenses (Press release, Aclaris Therapeutics, OCT 22, 2018, View Source [SID1234530061]). All of the common stock in the offering was sold by Aclaris.

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Leerink Partners and Evercore ISI acted as joint book-running managers for the offering. Cantor acted as lead manager for the offering. Guggenheim Securities acted as co-manager for the offering.

A shelf registration statement relating to this offering was filed with the Securities and Exchange Commission (SEC) on November 2, 2016 and declared effective by the SEC on November 14, 2016. The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A final prospectus supplement and accompanying prospectus relating to the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained by contacting Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, telephone: (800) 808-7525, ext. 6132, or by email at [email protected]; or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, New York 10055, by telephone at 888-474-0200, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On October 22, 2018 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported updated preliminary results from a Phase 2 clinical trial of its lead product candidate, tipifarnib, in squamous cell carcinomas with HRAS mutations (Press release, Kura Oncology, OCT 22, 2018, View Source [SID1234530048]). The results are being presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich. A copy of the presentation is available online at www.kuraoncology.com.

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As of the September 7, 2018 clinical data cutoff date, 17 patients with HRAS mutant head and neck squamous cell carcinomas (HNSCC) were enrolled in the ongoing Phase 2 trial. Tumor size reductions were observed in nine of 11 evaluable patients, with five confirmed partial responses (PRs) as defined by standard RECIST criteria, including three patients with durable responses lasting more than 17 months. A sixth patient achieved a confirmed PR after the data cutoff. Four patients had stable disease, including two patients who experienced prolonged disease stabilization lasting more than six months. Only one patient experienced progressive disease as best response.

Another patient with HRAS mutant HNSCC, who is currently being treated off-protocol, has been reported as an unconfirmed PR with a 40% tumor size reduction.

In addition, the ongoing Phase 2 trial enrolled six patients in an additional cohort of other HRAS mutant squamous cell carcinomas (SCCs). One of the two evaluable patients in this cohort achieved a confirmed PR. Four patients were not evaluable as of the data cutoff date, including two patients who were pending initial efficacy assessments.

An analysis of available tumor biopsy samples (n=20) indicated a significant association between the allele frequency of HRAS mutations and a patient’s best response to tipifarnib. Patients with HRAS mutant allele frequencies as low as 1% were treated with tipifarnib. Of the 13 HNSCC/SCC patients with a tumor HRAS mutant allele frequency greater than 20%, six achieved PRs, one achieved an unconfirmed PR and is ongoing, and two experienced disease stabilization greater than six months. No meaningful clinical benefit was observed in the seven patients with an allele frequency less than 20%. Data from The Cancer Genome Atlas (TCGA HNSCC, provisional) indicate that patients with an HRAS mutant allele frequency greater than 20% represent approximately 5% of the overall HNSCC population.

"The results from this study indicate that tipifarnib is active in this difficult-to-treat population, with rapid and durable responses independent of prior therapy," said Alan Ho, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center and principal investigator of the study. "These data are particularly encouraging when we consider the high unmet need for patients with recurrent, metastatic head and neck squamous cell carcinomas, despite the introduction of immunotherapy into the treatment paradigm."

Response rates for the three therapies approved for treatment of HNSCC in the second line, Keytruda (pembrolizumab), Opdivo (nivolumab) and Erbitux (cetuximab), range from 13-16%, with progression-free survival of approximately two months.

Patients in the Phase 2 trial of tipifarnib in HRAS mutant HNSCC had a median of two prior lines of therapy (range 1-5), with confirmed responses observed in patients who had progressed on cetuximab regimens, immunotherapy or both.

Dose-limiting, treatment-emergent adverse events in the trial included hematological events and gastrointestinal disturbances, which were managed by dose interruption and/or dose reduction. When dose interruption/delay is taken into account, the median dose received by trial patients across all three cohorts was determined to be 600 mg twice daily by Cycle 2. Four of the responses in the trial were achieved at the 600 mg dose, including one patient who started dosing at 600 mg due to frailty and experienced a PR, and three patients who were dose-reduced to 600 mg and experienced a confirmed PR. Two additional patients achieved disease stabilization greater than six months.

Based on the observations from this Phase 2 trial, Kura intends to introduce a minimum tumor HRAS mutant allele frequency, anticipated to be no lower than 20%, as an entry criterion and use 600 mg orally twice daily as the starting dose in its upcoming AIM-HN registration-directed study of tipifarnib in HRAS mutant HNSCC. Kura also intends to implement these modifications in its ongoing Phase 2 trial and anticipates being able to provide additional data in 2019.

"We are very encouraged by the progress reported today in the treatment of patients with HRAS mutant squamous cell carcinomas," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "These data provide

preliminary clinical evidence of successful targeting of RAS-driven tumors. Notably, we observed a significant association between HRAS mutant allele frequency and objective response. We believe this finding represents a meaningful advancement in the field of precision medicine that will help our efforts to deliver on the promise of tipifarnib as a therapy for the treatment of HNSCC. We are applying these learnings to our upcoming registration-directed trial, which remains on track to initiate by year end."

Conference Call and Webcast

Kura’s management will host a webcast and conference call at 17:00 CET / 11:00 a.m. ET today, October 22, 2018, following the conclusion of Dr. Ho’s presentation at the ESMO (Free ESMO Whitepaper) 2018 Congress. The live call may be accessed by dialing (877) 516-3514 for domestic callers or (281) 973-6129 for international callers and using conference ID #6045389. A live webcast of the call will be available from the Investors and Media section of the company website at www.kuraoncology.com, and will be archived there for 30 days.

About Tipifarnib

Kura Oncology’s lead candidate, tipifarnib, is an inhibitor of farnesylation, a key cell signaling process implicated in cancer initiation and development. In extensive clinical trials, tipifarnib has shown compelling and durable anti-cancer activity in certain patient subsets. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, the company is seeking to identify those patients most likely to benefit from tipifarnib. In addition to its development program in solid tumors with HRAS mutations, Kura has identified the CXCL12 pathway and bone marrow homing of myeloid cells as potential biomarkers of activity for tipifarnib in certain hematologic malignancies. The company expects to present biomarker-enriched data from peripheral T-cell lymphomas (PTCL) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018.

On October 22, 2018 BerGenBio ASA (OSE:BGBIO) reported that the company and its collaborators have presented interim clinical and biomarker data from BerGenBio’s Phase II clinical programme with bemcentinib (BGB324), a first-in-class highly selective oral AXL inhibitor at the ESMO (Free ESMO Whitepaper) 2018 Congress in Munich (19 – 23 October 2018). Additionally, a pre-clinical study in myelodysplastic syndrome (MDS) was presented (Press release, BerGenBio, OCT 22, 2018, View Source [SID1234530046]).

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The posters are available at www.bergenbio.com in the Investors / Presentations section and a summary of results is given below.

(1) Poster Discussion: Predictive and Pharmacodynamic Biomarkers Associated with Phase II, selective and orally bioavailable AXL Inhibitor Bemcentinib Across Multiple Clinical Trials
Bob Holt et al

The poster discussed the broad biomarker programme run in parallel to the phase II clinical trial programme with bemcentinib and detailed some of the key findings to date:

Tumour AXL expression predicts patient benefit: 7 out of 10 second line NSCLC patients show clinical benefit (70% CBR) including 4 responses (40% ORR) on KEYTRUDA/bemcentinib combination therapy (determined by BerGenBio’s proprietary immunohistochemistry method).
Blood based biomarkers, including soluble AXL, have been found predictive of patient benefit in relapsed/refractory AML/MDS & NSCLC
(2) Poster Presentation: Update on the randomised Phase Ib/II study of the selective small molecule AXL inhibitor bemcentinib (BGB324) in combination with either dabrafenib/trametinib or pembrolizumab in patients with metastatic melanoma
Cornelia Schuster et al

The poster gave an update on the randomised trial in first line metastatic melanoma, combining bemcentinib with standard of care therapies:

Confirmed recommended phase II dose of bemcentinib in combination with MEKINIST/TAFINLAR and KEYTRUDA.
All combinations continue to be well tolerated.
Efficacy is seen across all arms with 18 out of 23 radiographically evaluated patients reporting clinical benefit including complete responses.
(3) Poster Discussion: The identification of the AXL/Gas6 signalling axis as a key player of myelodysplastic syndrome (MDS) and the potential of the oral selective AXL inhibitor bemcentinib in the treatment of MDS
Hind Medyouf et al

The poster discussed the relationship between AXL and myelodysplastic syndrome using both patient samples and animal model studies. The data show that AXL is upregulated in MDS patients and that inhibiting AXL with bemcentinib shows efficacy in pre-clinical models of the disease.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "The ability to predict which patients are most likely to derive benefit from treatment is an important competitive advantage as it is key to improving patient outcomes and regulatory success. The data presented at ESMO (Free ESMO Whitepaper) increases our confidence in the predictive nature of our proprietary biomarkers and diagnostics. What is more, 7 out of 10 AXL positive NSCLC patients showed clinical benefit in our phase II trial combining bemcentinib with KEYTRUDA, this is a remarkable observation and gives us confidence in bemcentinib’s proposed mechanism of action. Additionally, data presented at ESMO (Free ESMO Whitepaper) continue to show that bemcentinib is well tolerated and effective across our broad phase II combination program. We are looking forward to provide further updates on the development of our AXL inhibitor pipeline over the coming months."

– END –

About the ESMO (Free ESMO Whitepaper) Congress
The ESMO (Free ESMO Whitepaper) Congress is the leading European meeting for medical oncology convening over 26,000 international delegates from the field. ESMO (Free ESMO Whitepaper) 2018 will be held in Munich, Germany 19 – 23 October 2018.

About BerGenBio’s Companion Diagnostics programme
In parallel with its phase II clinical trial programme, BerGenBio explores predictive biomarker candidates with the aim to develop a companion diagnostic to identify patients most likely to benefit from bemcentinib treatment.

Thus far, the company reported strong correlation with response of both plasma soluble AXL levels and the presence of tissue AXL in relapsed/refractory AML or MDS and advanced NSCLC, respectively.

About the BGBC008 trial
The BGBC008 trial is a phase II multi-centre open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated, immunotherapy na’fve, patients with advanced adenocarcinoma of the lung, the most common form of non-small cell lung cancer (NSCLC). The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

For more information please access trial NCT03184571 at www.clinicaltrials.gov.

About the BGBIL006 trial
The BGBIL006 trial is a randomised Phase 1b/2 clinical study of bemcentinib (BGB324) in combination with either the MAPK inhibitors MEKINIST (trametinib) plus TAFINLAR (dabrafenib) or the immune checkpoint inhibitor KEYTRUDA (pembrolizumab) in patients with advanced melanoma.

On October 22, 2018 AVEO Oncology (NASDAQ:AVEO) and EUSA Pharma reported the presentation of updated interim results from the Phase 2 portion of the TiNivo study, a Phase 1b/2 multicenter trial of oral (PO) tivozanib (FOTIVDA) in combination with intravenous (IV) nivolumab (OPDIVO, Bristol-Myers Squibb), an immune checkpoint, or PD-1, inhibitor, for the treatment of advanced or metastatic renal cell carcinoma (Press release, AVEO, OCT 22, 2018, View Source [SID1234530044]). The results were presented today at European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Congress, in a poster presentation titled "TiNivo: Tivozanib Combined with Nivolumab: Safety and Efficacy in Patients with Metastatic Renal Cell Carcinoma (mRCC)" (Presentation 878P). A copy of the presentation is available at www.aveooncology.com or further information can be obtained via EUSA Pharma Medical Information.

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The Phase 1b/2 study has enrolled a total of 28 patients. The Phase 2 portion of the study (n=22) was designed to assess the safety, tolerability, and anti-tumor activity of the full dose and schedule of PO tivozanib (1.5 mg/QD for 21 days followed by a 7-day rest period), as established in the Phase 1b portion of the study (n=6), in combination with IV nivolumab (240 mg every 2 weeks). The combination was generally well tolerated. Treatment-related Grade 3/4 adverse events occurred in 60% of patients, the most common of which was hypertension.

Interim efficacy was assessed in all 25 patients treated with the full dose and schedule of PO tivozanib in combination with IV nivolumab and enrolled at least 4 months prior to the data cutoff date. Of these, 13 (52%) had received at least one prior systemic therapy. An objective response rate was observed in 56% of patients (complete responses + partial responses), including 4% of patients (n=1) achieving a complete response, and a disease control rate (complete response + partial response + stable disease) was observed in 96% of patients. At the time of data collection 52% (n=13), of patients remained on study. To date, a total of 72% of patients (n=18) had tumor shrinkage of ≥25%, with a majority of patients having disease control for ≥48 weeks.

"With high and durable tumor shrinkage rates for the combination of tivozanib and nivolumab, including a complete response, coupled with a favorable tolerability profile and nearly all patients having disease control, the TiNivo study continues to underscore a compelling rationale for using a high-specificity VEGF inhibitor as the TKI of choice in immuno-oncology combinations," Doctor Bernard Escudier, MD, ex-Chairman of the Genitourinary Oncology Committee, Gustave Roussy, and lead investigator of the study. "The ability to give a VEGF inhibitor and immuno-oncology agent both at full dose and strength could serve to deliver both improved outcomes and an improved patient experience. I look forward to better understanding tivozanib’s potential in immunotherapy combinations through a larger randomized study, which is currently being planned."

"There are multiple cancers where IO-TKI combinations have demonstrated potential, and the favorable tolerability and efficacy outcomes seen in the TiNivo study make further exploration of these indications a priority for AVEO," said Michael Bailey, president and chief executive officer of AVEO. "We continue to build out a clinical strategy for studying such combinations, and look forward to outlining our plans following reporting of topline data from our Phase 3 TIVO-3 study, which is expected in the mid-fourth quarter."

"The data arising from combination studies with checkpoint inhibitors demonstrate the considerable potential for tivozanib in metastatic RCC," said Lee Morley, Chief Executive Officer of EUSA Pharma. "EUSA continues to launch tivozanib across the EU in line with its EMA approval as monotherapy in the first line setting where its efficacy and favorable tolerability profile continue to provide benefits to patients, and we are excited by the prospect of further development of tivozanib as part of a future IO-TKI treatment option."

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models, enabling potentially enhanced activity when used in combination with immune modulating therapy.3 As part of a North American registration plan, tivozanib is currently being studied in the Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory RCC. Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.