On October 22, 2018 Aeglea BioTherapeutics, Inc. (NASDAQ: AGLE), a clinical-stage biotechnology company that designs and develops innovative human enzyme therapeutics for patients with rare genetic diseases and cancer, reported that it presented positive clinical data for pegzilarginase in melanoma patients at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany (Press release, Aeglea BioTherapeutics, OCT 22, 2018, View Source [SID1234530029]). The poster, titled "Initial cohort expansion results of sustained arginine depletion with Pegzilarginase in melanoma patients in a phase 1 advanced solid tumor trial," was presented on October 21. Clinical data from the Company’s ongoing Phase 1 clinical trial investigating pegzilarginase as a single agent includes expansion cohorts for cutaneous melanoma and uveal melanoma.

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"This ongoing clinical study of pegzilarginase demonstrated single agent anti-tumor activity in what is a difficult-to-treat population of heavily pre-treated melanoma patients," said James Wooldridge, M.D., chief medical officer of Aeglea. "These findings are in line with expectations from our single agent preclinical studies. Given the significant synergies we observed in preclinical studies with immune checkpoint inhibitors, we look forward to data readouts from the Phase 1/2 combination clinical trial."

Data highlights from ESMO (Free ESMO Whitepaper) 2018:

Pegzilarginase demonstrated single agent anti-tumor activity in patients with advanced melanoma

–Of the 28 patients included in the two cohorts, there was one confirmed partial response (PR) and eight patients with stable disease (SD). Six patients remained on treatment at the time of the data cutoff.
–Anti-tumor activity appeared greater in patients with tumors that lack ASS1 (argininosuccinate synthetase 1) expression, which is consistent with preclinical studies that suggest tumors lacking ASS1 expression are dependent on extracellular arginine for survival.

Pegzilarginase rapidly and sustainably depleted plasma arginine with a manageable safety profile, treatment related adverse events were grade three or lower
About Pegzilarginase in Cancer
Pegzilarginase is an enhanced human arginase that enzymatically degrades the amino acid arginine. In some cancers, tumor cells stop producing specific amino acids and must acquire them from the blood, making the tumor cells susceptible to starvation through depletion of those amino acids. Aeglea is developing pegzilarginase to exploit vulnerabilities in some cancers that lead to an increased dependency on extracellular arginine. Pegzilarginase targets these arginine dependent cancers by depleting blood arginine levels to below the normal range. Preclinical data demonstrated that the resulting arginine starvation inhibits proliferation, induces cell death, increases turnover of cell components and promotes anti-tumor immune responses. The Company’s Phase 1 data in advanced solid tumors demonstrated that pegzilarginase was well tolerated at doses that produced marked and sustained reductions in blood arginine levels below the normal range.

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 21, 2018 IntelGenx Technologies Corp. (TSXV: IGX) (OTCQX: IGXT) (the "Company" or "IntelGenx") is pleased to announce that it has closed its offering (the "Offering") of 17,144,314 units (the "Units") at a price of US$0.70 (the "Offering Price") for gross proceeds of approximately US$12 million in the United States and the Canadian provinces of Alberta, British Columbia, Manitoba, Ontario and Quebec (Press release, IntelGenx, OCT 22, 2018, View Source [SID1234530112]).

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Each Unit consists of one share of common stock (the "Offered Shares") and one half of one warrant (a "Warrant"), each whole Warrant entitling the holder to purchase one share of common stock of the Company at an exercise price of US$1.00 per share. The Warrants are exercisable immediately and will expire on the third anniversary of the date of their issuance.

The Units were distributed under a final prospectus supplement to the U.S. registration statement on Form S-3 (File No. 333-227498) which was declared effective on October 15, 2018 (the "Registration Statement") and a final Canadian MJDS prospectus supplement to the Canadian MJDS short-form base shelf dated October 18, 2018 filed by the Company in connection with the Offering. Copies of the U.S. prospectus supplement and the Registration Statement can be obtained from the SEC’s website at www.sec.gov.

Copies of the final prospectus supplement and the Registration Statement may also be obtained from H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, by calling (646) 975-6996 or by emailing [email protected].

The Offering was conducted, on a best efforts basis, by H.C. Wainwright & Co. ("Wainwright"), in its capacity as the exclusive placement agent for the Units offered in the United States, and Echelon Wealth Partners Inc., in its capacity as the exclusive placement agent for the Units offered in Canada ("Echelon" and collectively with Wainwright, the "Agents").

The Company has granted Echelon an over-allotment option exercisable, in whole or in part, at the sole discretion of Echelon, at any time prior to 5:00 p.m. (Montreal time) on the date that is the 30th day after the closing of the date hereof, to purchase shares of common stock of the Company and/or Warrants in an amount representing up to an additional 15% of the number of Units sold pursuant to the Offering, at the Offering Price to cover over-allocations, if any, and for market stabilization purposes.

The TSX Venture Exchange (the "TSXV") has conditionally approved the listing of the common stock that will be issued by the Company in the Offering, including the shares of common stock issuable upon the exercise of the Warrants. Listing on the TSXV will be subject to the Company fulfilling all of the listing requirements of the TSXV within 30 days of the closing of the Offering.

After the payment of the Agents’ commissions and the reimbursement of certain of the Agents’ Offering expenses and the payment of other Offering expenses, the Company expects the net proceeds from the Offering to be approximately US$10.5 million. The Company intends to use the net proceeds from the Offering for its 2a Montelukast Study, its Tadalafil 505(b)(2) submission to the U.S. Food and Drug Administration, and working capital.

On October 22, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported the presentation of data from two clinical trials for PEGPH20 (pegvorhyaluronidase alfa) in patients with advanced pancreas and metastatic breast cancer (Press release, Halozyme, OCT 22, 2018, View Source [SID1234530030]). The presentations were made at the annual European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, taking place October 19-23 in Munich. PEGPH20 is Halozyme’s proprietary PEGylated recombinant human hyaluronidase enzyme that degrades hyaluronan (HA), a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in many solid tumors, potentially impeding the immune response and the access of anti-cancer therapies. PEGPH20 is being developed as an investigational new drug for the treatment of advanced pancreas cancer, specifically in patients with tumors that accumulate HA, referred to as HA-high.

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"These data reinforce the potential for PEGPH20 in combination with chemotherapy in these well-defined patient populations. It adds to the supportive evidence that suggests PEGPH20 could play a critical role in degrading tumor HA, allowing greater penetration of chemotherapy and improved access of the immune system into the tumor," said Dr. Helen Torley, president and chief executive officer of Halozyme. "PEGPH20 may provide a unique targeted approach for patients with late-stage cancers where new treatment options are needed."

Poster Presentations of PEGPH20 Clinical Studies at ESMO (Free ESMO Whitepaper) 2018

Abstract 5965/730P – A pilot study of gemcitabine, nab-paclitaxel, PEGPH20 and rivaroxaban for advanced pancreatic adenocarcinoma: interim safety and efficacy analysis
K. Yu, Memorial Sloan-Kettering Cancer Center, et al.

This investigator sponsored study has enrolled 60 patients with advanced pancreatic adenocarcinoma (PDAC), 42 patients without prior thromboembolic events (TE) in cohort 1 and 18 patients with prior TE in cohort 2. Patients received PEGPH20 (3 ug/kg, the same dose as is being evaluated in HALO-301), plus the standard dose and schedule for nab-paclitaxel (125 mg/m2), and gemcitabine (1000 mg/m2), plus rivaroxaban (15 mg PO BID for 21 days induction, then 20 mg PO QD), an oral anticoagulant that has been shown to reduce TE in patients receiving chemotherapy. The primary objective was the rate of symptomatic TE events, and the secondary objectives included PFS, OS and major bleeding rate.

All 60 patients are evaluable for safety and efficacy. Two (3%) grade 3/4 TE events occurred (one in each cohort), and two grade 3 GI hemorrhages; these AEs resolved with supportive treatment. There were three (5%) complete responses, 28 (47%) partial responses, 20 (33%) stable disease responses, and 9 (15%) progressive disease/non-evaluable responses. Median PFS is 7.0 months across both cohorts, and median overall survival has not been reached. Efficacy and safety are similar for patients with and without prior TE. Tissue biopsies have been collected to evaluate response by HA level but the analysis is not yet completed.

Abstract 5999/311P – Early results from an Open-label Phase 1b/2 study of eribulin mesylate (EM) + pegvorhyaluronidase alpha (PEGPH20) combination for the treatment of patients with HER2-negative, high-hyaluronan (HA) metastatic breast cancer (MBC)
M. Shum, The Oncology Institute Whittier, et al.

The Phase 1b portion of the study enrolled 14 patients with HER2 negative metastatic breast cancer without regard for HA status. Patients were treated with IV PEGPH20 plus eribulin mesylate (HALAVEN), a microtubule inhibitor approved for the treatment of metastatic breast cancer in patients previously treated with up to two lines of systemic anticancer therapy. Two different dose-levels of PEGPH20 (3ug/kg and 1.6ug/kg) were tested in combination with 1.4 mg/m2 EM. The data cut-off date for this analysis was February 2018. The median number of 21-day treatment cycles in this trial was six. No complete responses were reported, four (28.6%) patients had a partial response and three (21%) had stable disease. Drug related treatment emergent adverse events (TEAEs) occurred in 86% of patients, with 79% of patients experiencing grade 3 or higher TEAEs. There were three serious adverse events, and the overall safety profile for PEGPH20 + eribulin mesylate was in line with previous observations, with no new safety signals identified. As a result of dose limiting toxicities at the higher dose,1.6ug/kg was determined to be the appropriate dose for this combination. An additional response was confirmed following the data cutoff, increasing the overall response rate to 36%. The overall response rate is encouraging and the PEGPH20 + eribulin mesylate combination warrants further investigation.

About PEGPH20

PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase enzyme under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan (HA). PEGPH20 targets and degrades hyaluronan, a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in many solid tumors, potentially constricting blood vessels, impeding the immune response and the access of anti-cancer therapies. PEGPH20 is being studied in a Phase 3 trial in patients with late stage HA-high pancreas tumors.

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.