On January 3, 2019 Marker Therapeutics, Inc. (NASDAQ: MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported a year-end update in five clinical trials using the Company’s therapeutic products, LAPP and MAPP multi-antigen targeted T cell (MultiTAA) therapies and TPIV200, its Folate Receptor Alpha (FRα) peptide cancer vaccine product candidate (Press release, Marker Therapeutics, JAN 3, 2019, View Source [SID1234532426]).

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"We are pleased to provide an update on our progress in advancing clinical trials using our therapeutic platform," stated Peter L. Hoang, President & CEO of Marker Therapeutics. "With our MultiTAA cell therapies, we continue to build on the size and depth of our patient dataset. These updates now bring our total reported number of patients to 72, up from 57 in our previously reported results. I believe this represents one of the most extensive sets of clinical results in cell therapy for cancer treatment and illustrates the potential safety and clinical effects of MultiTAA T cells for patients suffering from a number of terrible cancers."

"In our vaccine program, we continue to demonstrate our commitment to excellence in our clinical execution," Mr. Hoang continued. "Last year when I joined the company, I expressed that we would work to improve our clinical efficiency, and I believe that the completion of enrollment of our FRV-004 study in ovarian cancer over six months ahead of schedule reflects our dedication to that objective. In fact, we have now completed enrollment of our last two clinical trials significantly ahead of projections, reflecting the commitment of our management and clinical team to execute multi-center studies effectively."

The Company reported clinical updates in three Baylor College of Medicine (BCM)-sponsored Phase I/II clinical trials using its MultiTAA T cell therapies, LAPP and MAPP:

Lymphoma

In the Phase I/II clinical trial in lymphoma, BCM has now treated 15 patients with active disease who have failed an average of four lines of prior therapy. Of these patients, five patients experienced transient disease stabilization followed by disease progression. Four patients have ongoing stable disease of between 9 to 24+ months following infusion of the MultiTAA-specific T cells, while the remaining six have all had complete and durable responses (4 months to 60+ months), as assessed by PET imaging.

No relapses observed to date for any patient entering a complete response (CR).
Patients with active disease who have ongoing complete responses after infusion of MultiTAA cells are now between 1 and 5 years in CR (ongoing).
Several patients with stable disease show potential for durable disease stabilization, with two patients observed to have stable disease for over 9 months and 24 months, respectively.
Responses in all six patients who entered a CR were associated with an expansion of infused T cells as well as the induction of antigen spreading.
None of the treated patients developed cytokine release syndrome, neurotoxicity or any other infusion-related adverse events.
BCM has also treated 17 patients who had developed a CR following their last treatment (adjuvant therapy) for lymphoma, and all but two of these patients remain in remission (3-42 months post-infusion). Monitoring has continued on all patients previously reported, and none of these patients have yet relapsed with disease. Average duration of remission for patients with a continuing complete response (CCR) is over 26 months (ongoing), versus 16 months (ongoing) as of the last patient update.

Multiple Myeloma

Marker Therapeutics also provided an update to the BCM-sponsored Phase I/II clinical trial in multiple myeloma. Results were presented at an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting.

Ten patients with active disease were treated, including:
One patient with a CR durable for approximately 29 months before relapse, was subsequently given a second treatment infusion of MultiTAA T cells, resulting in stable disease for 3 months (ongoing) after the second treatment.
Two patients achieved partial responses (PR) of between 14 and 22 months (ongoing) as of last follow-up.
All seven remaining patients experienced stabilization of disease following infusion of MultiTAA cells initially. Three patients developed transient disease stabilization of between 3-7 months with subsequent progression, and four patients have ongoing stable disease.
Eight patients were treated in remission, with a median follow up of 21 months. Only one patient has relapsed to date.
Correlative studies show significant expansion of MultiTAA T cells, as well as significant evidence of epitope spreading with expansion of endogenous T cells specific for tumor-associated antigens that were not targeted by the MultiTAA product.
MultiTAA therapy appears to be safe and well-tolerated, with no incidence of cytokine release syndrome, neurotoxicity or any other serious adverse events related to the therapy.
Acute Lymphoblastic Leukemia

Marker Therapeutics also reported initial results from the BCM-sponsored Phase I clinical trial in acute lymphoblastic leukemia (ALL). In this study, patients were treated with MultiTAA T cells as a maintenance therapy for patients in CR post-allogeneic stem cell transplant. Leukemic relapse remains the major cause of treatment failure in hematopoietic stem cell transplant (HSCT) recipients.

10 patients have been enrolled and treated in this clinical trial, with eight patients evaluable for response. To date, all but one remains in CR, with patients ranging from 1 to 22 months in CCR (ongoing). Because of the highly refractory nature of these patients, the length of CCRs and the low rate of relapse amongst these patients, the Company believes that these early results are promising and may represent meaningful clinical benefit.
Marker Therapeutics also reported key updates from clinical studies of TPIV200, its Folate Receptor Alpha (FRα) peptide cancer vaccine product candidate.

Ovarian Cancer

Marker Therapeutics reported that it had completed enrollment in its Phase II study in ovarian cancer (Study FRV-004), using TPIV200 as a maintenance therapy for patients in their first remission after surgery and platinum-based chemotherapy. Marker has enrolled, randomized, and treated 120 patients at 17 clinical sites. The study completed enrollment six months faster than anticipated. The Company expects to reach its planned interim analysis trigger of 50 patients who have progressed by the end of the second quarter of 2019, with interim data reported by year end.

Enrollment of this study was completed over six months ahead of schedule, reflecting ongoing management initiatives to improve and enhance clinical operations efficiency.
Marker had previously projected the initiation of its interim analysis to begin in Q4 2018, triggered by the 50th patient to progress following treatment. Despite faster than expected enrollment of patients in this study, as of the end of December fewer than 50 patients had progressive disease. As a result, Marker now expects to reach its planned interim analysis trigger by end of the second quarter of 2019, with interim data reported by year end.
Triple Negative Breast Cancer

Marker Therapeutics also reported initial findings from its interim analysis of its dose-finding study (Study FRV-002) in patients with triple negative breast cancer, using TPIV200 as a maintenance therapy for patients in remission following first-line therapy. The four-arm study included low and high dose TPIV200 with or without cyclophosphamide.

Of 27 patients evaluated to date for immunogenicity, 26 showed significant immune response to the vaccine treatment. Of 80 patients treated at 11 clinical sites, 11 have shown disease progression to date following treatment with TPIV200.
"These additional clinical results strongly augment our existing, previously disclosed patient dataset. In patients who were treated for active disease in lymphoma, we continue to see long-lived, ongoing complete responses that are now durable beyond five years and have yet to observe a patient who achieves a CR subsequently relapse," said Dr. Richard Kenney, Acting Chief Medical Officer of Marker Therapeutics. "Notably, in the adjuvant lymphoma patients we have also not seen any additional relapses, with several patients now beyond four years in their continuing complete response. While the median progression-free survival has not yet been reached in any of these trials, observationally it appears that the time to progression for patients receiving MultiTAA T cell therapy may compare favorably with results reported in CD19 and BCMA-targeted CAR-T studies in lymphoma and multiple myeloma, without inducing the toxicities normally associated with gene-modified adoptive cell therapies."

"Given the highly refractory nature of the patients with acute lymphoblastic leukemia treated, we believe the preliminary results appear to be very promising, with only one patient having relapsed to date," continued Dr. Kenney. "These early results may indicate that MultiTAA therapy may be able to drive clinical benefit for these patients without the need for donor-lymphocyte infusions (DLIs), and the associated risk of graft versus host disease (GvHD). Finally, our clinical sites have been very supportive of our Phase II vaccine studies in ovarian and breast cancer, and their rapid enrollment is a credit to our Principal Investigators and clinical investigative sites, as well as our clinical operations team. We are pleased with the progress in building our clinical development infrastructure and believe we can leverage that experience to drive our upcoming MultiTAA T cell studies efficiently."

On January 3, 2019 Cydan reported the launch of Tiburio Therapeutics Inc. (Tiburio), a private biopharmaceutical company focused on developing treatments for rare neuroendocrine tumors and rare endocrine diseases (Press release, Cydan Development, JAN 3, 2019, View Source [SID1234553930]). Tiburio will advance two compounds licensed from Ipsen for the treatment of non-functioning pituitary adenoma (NFPA) (TBR-760) and for additional rare endocrine diseases (TBR-065). As part of the launch, Tiburio raised a $31M Series A financing that will fund the company’s lead compound, TBR-760, through human proof-of-concept for the treatment of NFPA and further clinical assessment of TBR-065 as a treatment for rare endocrine diseases. In conjunction with the Tiburio financing, Abraham N. Ceesay has been appointed chief executive officer of the company. Tiburio is the third orphan drug company launched by Cydan, an orphan drug accelerator dedicated to creating therapies to improve the lives of patients living with orphan diseases.

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"Patients suffering from rare neuroendocrine tumors and endocrine diseases represent a significantly underserved patient population due to the lack of effective treatment options," said Abraham N. Ceesay, chief executive officer of Tiburio. "TBR-760 and TBR-065 represent potential breakthroughs in the treatment of debilitating neuroendocrine diseases and we, at Tiburio, are intently focused on advancing these compounds for the benefit of patients. We will immediately begin Phase 2 enabling studies with TBR-760 and anticipate enrolling patients with NFPA in a Phase 2 study in the 2nd half of 2019."

The development of NFPA, which is a non-metastatic tumor in the pituitary gland in the brain, can result in life-altering and potentially life-threatening consequences for patients. Currently there are no approved therapies to treat these tumors and patients must undergo transsphenoidal surgery and/or radiation to remove or shrink the tumor. TBR-760 is a dopamine-somatostatin chimeric molecule that inhibits NFPA cell proliferation and has the potential to shrink or halt tumor growth. In prior clinical trials, TBR-760 has been shown to have a favorable safety profile.

"The agreement with Cydan to license these two innovative compounds to Tiburio expands upon the work we’ve done to advance them through Phase 2 trials, providing a foundation for their safety profile and mechanism of action," said Alexandre LeBeaut, MD, executive vice president, research & development and chief scientific officer, Ipsen. "The Cydan team’s expertise makes them a natural choice to partner with to ensure these programs can have impact for patients in need."

"Nonfunctioning pituitary adenoma can have a significant and lasting impact on patients, often requiring multiple surgeries to control tumor size, as well as radiation therapy. These invasive neurosurgeries are associated with high-risk complications," said Shi Yin Foo, MD, PhD, MMSc, chief medical officer of Cydan and acting chief medical officer of Tiburio. "There are no approved therapies and the current treatment options for these patients are invasive, risky, and often ineffective in the longer term. We can do better for patients and believe TBR-760 represents a potentially game-changing therapy for patients."

"TBR-760’s unique mechanism of action offers an exciting potential treatment for patients living with NFPA," said Chris Adams, co-founder and chief executive officer of Cydan. "Following an extensive review of the prior TBR-760 preclinical and clinical data, the Cydan team launched our third company, Tiburio, to execute a rapid clinical and regulatory program to bring this drug to patients in need."

Tiburio was granted an exclusive world-wide license to both TBR-760 and TBR-065. Ipsen will receive a minority ownership in the company as well as development and commercial milestone payments and royalties on sales. Tiburio is responsible for all future development and commercialization costs for both compounds. Additional financial terms were not disclosed.

Investment in the $31M Series A came from Cydan’s syndicate of leading life sciences investors, New Enterprise Associates, Longitude Capital, Lundbeckfonden Ventures, and Alexandria Venture Investments.

About NFPA

The pituitary gland, a master regulator of endocrine function, is located below the base of the brain. A nonfunctioning pituitary adenoma (NFPA) is a non-metastatic pituitary tumor that arise from gonadotroph cells in the pituitary. Patients often present with symptoms related to the size of the NFPA tumor, including headaches, vision problems, changes in milk production, weight change, menstrual changes, fatigue, sleep disruption, and depression or cognitive/behavioral changes.

Current treatment is limited to transsphenoidal surgery (TSS), which is performed through the nose and sinus passage, and/or radiation to halt the growth of these tumors. However, these two treatment options come with serious and high-risk consequences. In addition to these interventions designed to remove or reduce the size of the tumors, patients often require a complex set of medications to manage the endocrine disruption and other symptoms caused by the tumors and side effects of TSS and radiation.

In the U.S. there are approximately 5,000 new cases of NFPA that require TSS each year and 40-50% of these tumors will regrow within the first 5 years after surgery. Additionally, there are approximately 50,000 patients living with NFPA who may benefit from therapy to control tumor growth.

About Abraham Ceesay, CEO Tiburio

Mr. Ceesay has over 17 years of experience in leading biopharmaceutical companies and commercializing innovative therapeutic products. Prior to joining Tiburio, he served as chief operating officer at scPharmaceuticals where he developed and led all operational and commercial aspects of the company. Mr. Ceesay was integral in raising more than $140 million in private and public capital as well as closing the company’s initial public offering. Prior to joining scPharmaceuticals, he served as vice president, Sales, Marketing, and Commercial Operations at Keryx Biopharmaceuticals and spent four years at Ironwood Pharmaceuticals as Vice President of Marketing, and held responsibility for the management of the U.S. P&L, leadership of the Linzess brand team and co-promotion collaboration with Forest Laboratories/Allergan. Previously he was at Genzyme/Sanofi, initially as a field sales specialist and ultimately as the director, Renal Global Marketing, in which capacity he led the global launch of Renvela and held global marketing responsibility for the company’s renal franchise (Renagel, Renvela, Hectorol). Mr. Ceesay serves on the Board of Advisors for Life Science Cares and the Board of Directors for Food for Free. He holds a bachelor’s degree from Ithaca College, and a Master of Business Administration from Suffolk University’s Sawyer School of Management.

On January 3, 2019 Athenex, Inc. (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that it, through its subsidiary, has entered into a licensing and partnership agreement with Chongqing Jingdong Junzhuo Pharmaceutical Co., Ltd. ("Chongqing Jingdong Pharmaceutical") on December 30, 2018 to exclusively develop and commercialize KX2-391 for the treatment of actinic keratosis and oncology indications in humans in China (Press release, Athenex, JAN 3, 2019, View Source [SID1234534523]).

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KX2-391, also known as KX-01, is a first-in-class dual Src kinase and tubulin polymerization inhibitor. KX2-391 ointment is a topical medicinal product for the treatment of actinic keratosis that is in late stage Phase III development. Actinic keratosis is a common skin condition that is induced through ultra-violet light damage, resulting in patches of thick, scaly, or crusty skin. Left untreated, the lesions have risk of progression to squamous cell carcinoma and consequently treatment by a dermatologist is recommended. Other drug candidates with KX2-391 as the compound are also being developed for oncology indications.

Pursuant to the terms and conditions of the arrangement, Athenex will grant to Chongqing Jingdong Pharmaceutical an exclusive license under Athenex’s intellectual property to commercialize topical and oral products containing KX2-391 in mainland China, excluding Hong Kong, Macau and Taiwan. Athenex is expected to receive an upfront payment of an aggregate amount of US$14.5 million. Athenex will also be eligible to receive other development milestone payments of up to US$15 million. In addition, the agreement provides for tiered royalties based on annual net sales starting at 15%, and with incremental increases of royalties with increases in sales.

Athenex will be responsible for conducting all preclinical and clinical studies, as well as regulatory submissions, required for approval in China. Chongqing Jingdong Pharmaceutical will employ its expertise to plan and prepare for the commercialization of the products in China. Athenex announced on July 26, 2018 that statistical significance (p < 0.001) was achieved in two Phase III studies conducted in the United States to support the registration of KX2-391 ointment for the treatment of actinic keratosis. Athenex has submitted an abstract to the American Academy of Dermatology for potential presentation of top-line data from Phase III studies at the AAD meeting in March 2019.

Bin Li, Chief Executive Officer, Chongqing Jingdong Pharmaceutical, commented, "We are pleased to enter into this strategic collaboration with Athenex. We are excited with the very encouraging results generated from the two Phase III studies of KX2-391 ointment, and are impressed by the Athenex team in their innovation and execution of drug development efforts. KX2-391 ointment has the potential to change the standard of care for treatment of actinic keratosis and there is a large unmet medical need in China. We look forward to bringing this promising product to market in China, as well as other potential drug candidates. Our strength and capabilities in drug commercialization and our relationships with key stakeholders in both the pharmaceutical industry and healthcare system in China will complement Athenex’s drug development expertise."

Johnson Lau, Chief Executive Officer, Athenex, added, "Athenex is excited to partner with Chongqing Jingdong Pharmaceutical to develop and commercialize KX2-391. Chongqing Jingdong Pharmaceutical is a pioneer in pharmaceutical drug sales and distribution in China. We are impressed by the management team of Chongqing Jingdong Pharmaceutical and are confident that this partnership will create strong synergies and a platform for growth for both companies in China. Chongqing Jingdong Pharmaceutical’s experience and execution in the Chinese market will be critical to bringing our product to market in the country."

Athenex has a license agreement with Almirall, S.A. on the rights to KX2-391 ointment in the following territories: USA, European Union, Russia and Turkey. Details of this arrangement were disclosed in December 2017.

On January 3, 2019 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that it will participate at the Biotech Showcase 2019 conference and the BIO One-on-One Partnering @ JPM 2019, taking place between Monday, January 7th and Wednesday, January 9th, that will be held in San Francisco, California in parallel to the JP Morgan Healthcare Conference (Press release, Can-Fite BioPharma, JAN 3, 2019, View Source [SID1234532375]).

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Sari Fishman, VP of Business Development, will host partnering meetings at the two conferences with biotech and pharmaceutical companies.

Can-Fite’s near term milestones include data release from a Phase II study with its Namodenoson drug in patients with advanced liver cancer which is expected in Q1/19. In addition, the Company is actively enrolling NAFLD/NASH patients for a Phase II study of Namodenoson.

On January 3, 2019 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that Alan H. Auerbach, Chairman, Chief Executive Officer, President and Founder of Puma, will provide an overview of the Company at 12:00 Noon PST on Wednesday, January 9, at the 37th Annual J. P. Morgan Healthcare Conference (Press release, Puma Biotechnology, JAN 3, 2019, View Source [SID1234532394]). The conference will be held at the Westin St. Francis Hotel in San Francisco.

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A live webcast of the presentation will be available on the Company’s website at www.pumabiotechnology.com . The presentation will be archived on the website and available for 30 days