On November 13, 2018 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company applying synthetic biology to beneficial microbes to develop novel, living medicines, reported its financial results for the third quarter ended September 30, 2018, and provided an update on its programs (Press release, Synlogic, NOV 13, 2018, View Source [SID1234531263]).

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"This is an exciting time for Synlogic, as we continue to explore the breadth of our platform. We have advanced SYNB1891, our dual innate immune activator for the treatment of cancer into IND-enabling studies," said Aoife Brennan, M.B., B.Ch., Synlogic’s president and chief executive officer. "Our two orally administered Synthetic Biotic medicines, SYNB1618 for the treatment of phenylketonuria and SYNB1020 for the treatment of hyperammonemia, have demonstrated proof of mechanism in healthy volunteers and we look forward to clinical data from the ongoing clinical trials in patients in 2019."

Recent Highlights
Pipeline

Presentation of preclinical data highlighting potential of Synthetic Biotic medicines in immuno-oncology (IO) and declaration of first IO clinical candidate at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting. Data presented at the meeting demonstrate the platform’s potential for the treatment of cancer and inflammation and specifically highlight the unique advantages of Synlogic’s approach to stimulate the innate immune system. Based on preclinical data Synlogic is advancing SYNB1891, a STING-agonist producing synthetic biotic strain, into IND-enabling studies. Synlogic hosted an investor and analyst event at the SITC (Free SITC Whitepaper) annual meeting, featuring presentations by key opinion leaders (KOLs), and members of Synlogic management who outlined development plans for SYNB1891. A webcast of the event is available on the Synlogic website.
Presentation of preclinical data supporting continued development of SYNB1020 for the treatment of liver disease at the American Association for the Study of Liver Diseases (AASLD) annual meeting. Preclinical data were presented demonstrating dose dependent lowering of blood ammonia by Synthetic Biotic strains designed to consume ammonia and produce arginine in a rat bile duct ligation model confirming earlier preclinical observations in mouse models of liver disease. In addition, data were presented from studies conducted by Synlogic to establish ammonia measurement parameters and ammonia levels in healthy volunteers at clinical sites that are participating in Synlogic’s ongoing Phase 1b/2a clinical trial of SYNB1020 in patients with cirrhosis and elevated ammonia. Topline data from this clinical trial are now expected in mid-2019 due to slower than expected rates of initiation of clinical trial sites and patient enrollment.
Announcement of positive interim data from healthy volunteer (HV) arm of its ongoing Phase 1/2a clinical trial evaluating SYNB1618 for the treatment of Phenylketonuria (PKU): Data established a go-forward dose for the treatment arm in patients with PKU and demonstrated a statistically significant, dose-dependent effect on treatment-associated biomarkers, indicating proof-of-mechanism. Synlogic also published preclinical data identifying these same biomarkers in Nature Biotechnology, further supporting SYNB1618’s continued development. The Company continues to evaluate SYNB1618 in patients with PKU in its ongoing Phase 1/2a study and expects to report topline data from this trial in mid-2019.
Corporate

Appointed Aoife Brennan, M.B., B.Ch., as president and chief executive officer: Dr. Brennan had served as interim president and chief executive officer since May 2018 and joined Synlogic as chief medical officer in 2016.
Third Quarter 2018 Financial Results
As of September 30, 2018, Synlogic had cash, cash equivalents, and short-term investments of $132.6 million.

For the three months ended September 30, 2018, Synlogic reported a consolidated net loss of $10.7 million, or $0.43 per share, compared to a consolidated net loss of $11.9 million, or $1.66 per share, for the corresponding period in 2017.

Research and development expenses were $9.9 million for the three months ended September 30, 2018 compared to $9.0 million for the corresponding period in 2017.

General and administrative expenses for the three months ended September 30, 2018 were $3.4 million compared to $3.2 million for the corresponding period in 2017.

Revenues were $1.8 million for the three months ended September 30, 2018, compared to $0.1 million for the corresponding period in 2017. The revenue for both periods is associated with Synlogic’s collaboration with AbbVie to develop a Synthetic Biotic medicine for the treatment of inflammatory bowel disease. The increase in revenue was primarily the result of the achievement of a $2.0 million milestone under a September 2018 amendment to the AbbVie agreement of which $1.8 million was recognized in revenue in the quarter ended September 30, 2018.

Nine-months Results
For the nine months ended September 30, 2018, the consolidated net loss was $36.5 million, or $1.56 per share, compared to a consolidated net loss of $28.7 million, or $7.87 per share, for the corresponding period in 2017.

Total operating expenses were $40.9 million for the nine months ended September 30, 2018, compared to $31.2 million for the corresponding period in 2017. The increase in operating expenses was primarily due to compensation-related expenses associated with increased headcount and increased external costs associated with development of Synlogic’s Synthetic Biotic programs.

Conference Call & Webcast Information
Synlogic will host a conference call and live webcast today at 5:00 p.m. ET today, Tuesday, November 13, 2018. To access the live webcast, please visit the "Event Calendar" page within the Investors and Media section of the Synlogic website. Alternatively, investors may listen to the call by dialing +1 (844) 815-2882 from locations in the United States or +1 (213) 660-0926 from outside the United States. The conference ID number is 2674209. For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors and Media section of the Synlogic website.

On November 13, 2018 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported new positive interim data from its TACTI-mel Phase I clinical trial, presented at the 33rd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in Washington, D.C., U.S (Press release, Immutep, NOV 13, 2018, View Source [SID1234531297]).

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The TACTI-mel study is evaluating the use of eftilagimod alpha ("efti" or "IMP321"), a soluble LAG-3Ig fusion protein based on the LAG-3 immune control mechanism, in combination with anti-PD-1 therapy KEYTRUDA (pembrolizumab) for unresectable or metastatic melanoma.

In an oral presentation, Prof. Adnan Khattak, Consultant Medical Oncologist at Fiona Stanley Hospital and a principal investigator of the on-going TACTI-mel study, showed efficacy and safety data from 18 patients in part A, the dose escalation part of the study, and first safety data from 6 patients in part B.

In part A, dose escalation, combination therapy started after four cycles of KEYTRUDA monotherapy. In part B, patients were treated with the combination from the first day of treatment i.e. receiving efti from day one, cycle one with KEYTRUDA.

The efficacy data from part A was encouraging and supportive of previously disclosed response rates with a 33% Overall Response Rate (ORR) when measured from start of the combination at cycle 5 of KEYTRUDA. The ORR was 61% when measured from the start of KEYTRUDA monotherapy treatment in an explorative analysis measuring from cycle 1, day 1. A disease control rate of 66% was reported from the combination treatment. The patient population was partly pre-treated before the start of KEYTRUDA, suboptimally responding to KEYTRUDA and the majority had increased risk factors.

In both parts (A and B), combination therapy has been well tolerated with no dose-limiting toxicities and local erythema and injection site reactions as the most common side effects. Importantly the safety data of part B supports the dose scheduling of the Company’s planned Phase II TACTI-002 clinical study in collaboration with MSD.

Dr. Frédéric Triebel, Immutep’s Chief Scientific Officer and Chief Medical Officer, also commented "We were honored to have been selected for an oral presentation of the data which further supports our hypothesis that combining efti with a checkpoint inhibitor results in a combinatory therapeutic benefit to patients, pushing the accelerator and releasing the brake of the immune system. The data also highlights the excellent safety profile of efti, when combined with an anti-PD-1 therapy."

Prof. Adnan Khattak commented, "We are very pleased with the responses we have observed in this patient population. These patients had a sub-optimal response to pembrolizumab monotherapy. However, after participating in the TACTI-mel study, we have seen good responses in these patients, with a very encouraging overall response rate."

The data was also presented in a poster presentation titled "Results from a Phase I dose escalation trial (TACTI-mel) with the soluble LAG-3 protein (IMP321, eftilagimod alpha) together with pembrolizumab in unresectable or metastatic melanoma."

The trial design of the Company’s planned Phase II TACTI-002 clinical study in collaboration with MSD was presented at SITC (Free SITC Whitepaper) in a poster titled, "A Multicenter, Phase II Study in Patients With First Line NSCLC, or Recurrent PD-X Refractory NSCLC or With Recurrent HNSCC Receiving Eftilagimod Alpha in Combination With Pembrolizumab (TACTI-002)".

Dr. Frédéric Triebel, Immutep’s Chief Scientific Officer and Chief Medical Officer, commented, "We are looking forward to the initiation of TACTI-002 later this year and I believe the clinical trial collaboration and supply agreement that we entered into with MSD earlier this year, as well as the recently announced agreement with Merck KGaA and Pfizer Inc., further supports the development of efti in combination with PD-1 and PD-L1 therapeutics."

The TACTI-mel poster and presentation, along with the TACTI-002 poster are available on Immutep’s website under the "Investor & Media" tab at www.immutep.com/investors-media/presentations.

About the TACTI-mel clinical trial

The ongoing TACTI-mel (Two ACTive Immunotherapies in melanoma) Phase I clinical trial is a multi-center, open-label, dosing escalating (1, 6 or 30 mg of eftilagimod alpha or "efti") study evaluating the combination of efti with pembrolizumab, in unresectable or metastatic melanoma patients that have had either a suboptimal response or had disease progression with pembrolizumab monotherapy (clinicaltrials.gov identifier NCT 02676869).

In Part A of the study, the combination therapy starts at treatment cycle 5 (of pembrolizumab) for 6 months and consists of three cohorts of six patients. Part B is an expansion of the initial study by an additional cohort of 6 patients that receive 30 mg of efti in combination with pembrolizumab starting at cycle 1 and with a treatment duration of 12 months.

On November 12, 2018 Ziopharm Oncology, Inc. (Nasdaq: ZIOP), reported that it has entered into definitive securities purchase agreements for the sale of its common stock and warrants to purchase common stock in a private placement that is expected to result in gross proceeds to the Company of approximately $50 million, before deducting placement agent and other offering expenses (Press release, Ziopharm, NOV 12, 2018, View Source [SID1234531224]). The private placement is being led by existing stockholder, MSD Partners, L.P. Other participants include Miller Value Partners, White Rock Capital Management and Level One Partners, LLC.

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Pursuant to the terms of the securities purchase agreement, at the closing of the private placement, Ziopharm will issue and sell 18,939,394 shares of common stock and warrants to purchase up to 18,939,394 additional shares of common stock at a per unit purchase price of $2.64. The warrants will become exercisable on the date that is six months following the date of issuance, have a per share exercise price of $3.01 and will expire five years from the date of issuance. The private placement is expected to close on or about November 13, 2018, subject to the satisfaction of customary closing conditions. Additional details regarding the private placement will be included in a Form 8-K filed by Ziopharm with the Securities and Exchange Commission (the "SEC").

Neither the shares of Ziopharm common stock nor the warrants to be issued in the private placement have been registered under the Securities Act of 1933, as amended (the "Securities Act"). Accordingly, these securities may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. Ziopharm has agreed to file a registration statement with the SEC to register the resale of Ziopharm common stock to be issued in the private placement as well as the Ziopharm common stock issuable upon exercise of the warrants.

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

On November 12, 2018 Cellectar Biosciences, Inc. (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted an exemption to the Import Alert placed on the Centre for Probe Development and Commercialization (CPDC), the sole supplier of the CLR 131 (Press release, Cellectar Biosciences, NOV 12, 2018, View Source [SID1234531227]). The exemption for CLR 131 is effective immediately for all hematology studies and, in response, Cellectar is preparing to dose patients in the second fractionated dose cohort of the Phase 1 relapsed refractory (R/R) multiple myeloma study and the Phase 2 study for R/R hematologic malignancies. The company awaits authorization from the FDA for any future shipments in connection with its Phase 1 study of pediatric patients with neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors.

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"We thank the FDA for their diligence and for providing this exemption for CLR 131 hematology studies. Our ability to advance our clinical trials and achieve stated business objectives remains our top priority," said James Caruso, president and CEO of Cellectar Biosciences. "I also want to recognize our team for their outstanding execution in support of a rapid resolution."

In its efforts to obtain an exemption for CLR 131 from the Import Alert in hematology and pediatrics, Cellectar has collaborated with the various divisions within the FDA that oversee the company’s investigational new drug applications evaluating CLR 131 in multiple indications. Cellectar executed a series of actions requested by the FDA to obtain an exemption to the Import Alert for its hematology programs. Similarly, the company continues to work with the appropriate division of the FDA to secure an exemption for the pediatric program.

As background, on August 10, 2018, Cellectar announced that CPDC was informed of an FDA Import Alert that prohibited CPDC from supplying CLR 131. While the Import Alert disrupted CLR 131 supply, the basis of the Import Alert was not related to CLR 131 specifically, or to CPDC’s production facility associated with CLR 131. The company actively supported CPDC’s efforts to have the Import Alert lifted as quickly as possible. The FDA subsequently initiated direct talks with Cellectar concerning a possible exemption for CLR 131 from the Import Alert. Those discussions and subsequent actions resulted in the exemption Cellectar is announcing today.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in relapsed/refractory multiple myeloma (R/R MM) and a range of B-cell malignancies, and a Phase 1b clinical study in patients with R/R MM exploring fractionated dosing. The objective of the multicenter, open-label, Phase 1b dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2 as well as a fractionated dose of 15.625 mCi/m2 given twice over seven days in Cohort 5. All study doses and regimens have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma as well as a second Phase 1 study in combination with external beam radiation for head and neck cancer.

On November 12, 2018 AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) reported that the US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for Priority Review for the use of Lynparza (olaparib) tablets as a maintenance treatment in patients with newly-diagnosed, BRCA-mutated (BRCAm) advanced ovarian cancer who were in complete or partial response following 1st-line standard platinum-based chemotherapy (Press release, AstraZeneca, NOV 12, 2018, View Source [SID1234531207]). A Prescription Drug User Fee Act (PDUFA) date is set for the first quarter of 2019.

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This is the first US regulatory submission acceptance for a poly ADP-ribose polymerase (PARP) inhibitor in the 1st-line maintenance setting for advanced ovarian cancer, and if approved will be the fourth indication for Lynparza in the US.

This submission was based on positive results from the pivotal Phase III SOLO-1 trial. The trial showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) for Lynparza compared to placebo, reducing the risk of disease progression or death by 70% in patients with newly-diagnosed, BRCAm advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy (HR 0.30 [95% CI 0.23-0.41], p<0.001). Of those receiving Lynparza, 60% remained progression-free at 36 months compared to 27% of women in the placebo arm. These data were recently presented for the first time at the ESMO (Free ESMO Whitepaper) 2018 Congress (European Society for Medical Oncology) and published online in the New England Journal of Medicine.

Lynparza is currently approved in over 60 countries for the treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is also approved in several countries, including the US and Japan, for germline BRCAm HER2-negative metastatic breast cancer – regulatory reviews are underway in the EU, Japan and other markets.

About SOLO-1

SOLO-1 is a Phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of Lynparza tablets (300mg twice daily) as maintenance monotherapy compared with placebo, in newly-diagnosed patients with BRCAm advanced ovarian cancer following platinum-based chemotherapy. The trial randomised 391 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy. Patients were randomised (2:1) to receive Lynparza or placebo for up to two years or until disease progression (at the investigator’s discretion). The primary endpoint was PFS and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival.

About Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP-enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death. Lynparza is being tested in a range of DDR-deficient tumour types.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

About ovarian cancer

Ovarian cancer is a leading cause of cancer death in women worldwide, with a five-year survival rate of 19%.[i] In 2018, there were over 295,000 new cases diagnosed and around 185,000 deaths.[ii] For newly-diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission or cure.[iii],[iv],[v],[vi]

About BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.