On January 25, 2019 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, reported that it has appointed Theradex Oncology, a global contract research organization ("CRO") with extensive expertise in oncology clinical development, as CRO for the planned phase I study of ATOR-1015 for the treatment of metastatic cancer (Press release, Alligator Bioscience, JAN 25, 2018, View Source [SID1234538681]). The study is expected to commence in the second half of 2018.

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The upcoming clinical phase I study with ATOR-1015 is a first-in-human dose escalation study in patients with metastatic cancer. The study will be conducted at five sites in Sweden and Denmark.

"Engaging Theradex is a key step towards starting our clinical phase I study with ATOR-1015 later this year", said Per Norlén, CEO of Alligator Bioscience. "We have worked previously with Theradex on the ADC-1013 clinical phase I trial and, based on their robust delivery and extensive expertise in clinical oncology research, we are confident in their ability to assist us in executing high-quality studies and we look forward to continuing our successful collaboration".

ATOR-1015 is a first-in-class bispecific antibody that targets CTLA-4 and OX40 and was created with Alligator’s unique bispecific technology. Alligator has advanced ATOR-1015 through preclinical development and is now preparing for the start of a clinical phase I study. Production of clinical trial material has already been completed and the final clinical trial authorization ("CTA") enabling activities required for study initiation will be completed in H1 2018.

For further information, please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 286 44 95
E-mail: [email protected].

The information was submitted for publication, through the agency of the contact person set out above, at 08:30 a.m. CET on 25 January 2018.

About ATOR-1015
ATOR-1015 is a next generation CTLA-4 bispecific antibody developed for tumor-directed immunotherapy with increased capability of regulatory T-cell depletion. It is fully owned by Alligator. ATOR-1015 binds to two different immune receptors: the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. The immune activation is increased in areas where both target molecules are expressed at high levels, notably in the tumor microenvironment, which is believed to reduce adverse immune reactions.

On January 25, 2018 Synthon Biopharmaceuticals (‘Synthon’) reported that the U.S. Food & Drug Administration (FDA) has granted Fast Track designation for its investigational anti-HER2 antibody-drug conjugate (ADC) [vic-]trastuzumab duocarmazine (SYD985) (Press release, Synthon, JAN 25, 2018, View Source [SID1234523560]). This designation is for treating patients diagnosed with HER2-positive metastatic breast cancer (MBC) that has progressed during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease, or progressed during or after [ado-]trastuzumab emtansine treatment.

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U.S. FDA Fast Track designation is one of four programs that are intended to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious or life threatening condition.

Fast Track designation for [vic-]trastuzumab duocarmazine was granted based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part Phase I clinical trial (SYD985.001). The positive clinical results indicate that this HER2-targeting ADC is efficacious and safe and could therefore provide substantial benefit to patients with no other treatment options.

In November 2017, Synthon initiated the pivotal Phase III TULIP trial, a multi-center, open-label, randomized clinical trial comparing the efficacy and safety of the ADC
[vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. Patients are currently being enrolled in this trial, which will be conducted in up to 100 sites in the United States, Canada, Europe and Singapore.

Dr. Jacques Lemmens, chief executive officer of Synthon, commented: "We are very pleased with this Fast Track designation for [vic-]trastuzumab duocarmazine based on the promising Phase I data. There is a high unmet medical need in patients that have HER2-positive MBC and have progressed on trastuzumab and [ado-]trastuzumab emtansine. I believe that the benefit/risk balance of [vic-]trastuzumab duocarmazine is favorable and that it can provide extended benefit to these patients. Fast Track designation will support efficient development and review of [vic-]trastuzumab duocarmazine and enable early access of this promising new single-agent therapy option."

On January 25, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that data from the investigator-initiated study evaluating the Company’s proprietary Lm-based antigen delivery product, axalimogene filolisbac (ADXS11-001), in combination with chemoradiation as a treatment for high-risk, locally advanced anal cancer were published in the International Journal of Radiation Oncology in an article titled, "Tolerability of ADXS11-001 Lm-LLO Listeria Based Immunotherapy With Mitomycin, Fluorouracil and Radiation for Anal Cancer (Press release, Advaxis, JAN 25, 2018, View Source [SID1234523562])."1 The abstract is available on-line here.

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The Phase 1 study, led by Dr. Howard Safran at Brown University, evaluated the safety and preliminary efficacy of the combination of ADXS11-001 with mitomycin, FU and intensity modulated radiation therapy in 10 patients with locally advanced, non-metastatic squamous cell anal cancer. Results showed that 9 patients achieved a complete response, and 8 patients (89%) remained disease free at a median follow-up of 42 months. One patient progressed, approximately 6 months post completion of study treatment and subsequently died from progressive disease, and one patient expired early in the study unrelated to study treatment.

Treatment-related adverse events were consistent with the observed safety profile of ADXS11-001, and consisted of mostly grade 1-2 cytokine-release related events such as chills, headache and fever. Two patients experienced grade 3 treatment-related toxicities. There were no grade 4 events and ADXS11-001 did not cause any additive chemoradiation related toxicities. All adverse events occurred within 24 hours of treatment and resolved with standard care.

These data show that ADXS11-001 can be safely administered with standard chemoradiation for patients with locally advanced, non-metastatic anal cancer.

"We are delighted to have these promising data highlighted in this prestigious, peer-reviewed journal. The complete clinical response demonstrated in patients who completed the combination treatment is very encouraging, particularly as there are limited treatment options or therapies under development for patients suffering with anal cancer," said Anthony Lombardo, interim Chief Executive Officer of Advaxis. "We look forward to advancing this promising therapy for anal cancer through investigator-led studies."

On January 25, 2018 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 it has received its first payment of approximately $2,200,000 from Gebro Holding GmBH (Press release, Can-Fite BioPharma, JAN 25, 2018, View Source [SID1234523563]). Can-Fite recently announced entering into a distribution agreement with Gebro for the exclusive right to distribute to distribute Can-Fite’s lead drug candidate, Piclidenoson (CF101), for the treatment of rheumatoid arthritis and psoriasis in 3 European countries including Spain, Switzerland and Austria, upon receipt of regulatory approvals. The recently signed Gebro distribution agreement adds to the distribution agreements for Piclidenoson that the company already has in place with Cipher Pharmaceuticals (for the distribution of Piclidenoson in Canada for rheumatoid arthritis and psoriasis) and Kwang Dong Pharmaceutical (for the distribution of Piclidenoson in Korea for rheumatoid arthritis).

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Under the terms of the distribution agreement, Gebro is making a total upfront and milestone payment of approximately $2,200,000 to Can-Fite. In addition, the agreement provides that additional payments of up to approximately $7,000,000 will be received by Can-Fite upon the achievement of certain regulatory, launch and sales milestones plus double digit royalty payments on net sales.

Gebro Pharma is a privately-owned leading pharma group founded in Austria in the late 1940s with over 500 employees. Its headquarters are located in Fieberbrunn (Austria), where Gebro is a top local leading player, with commercial operations in Spain and Switzerland. In Spain, Gebro is ranked among the top growing companies within the Pharma sector. The therapeutic focus of Gebro is pain with a strong franchise in rheumatology and in Spain, Gebro is ranked nº1 in rheumatology and pain. Alongside, rheumatology and pain, Gebro has also built a portfolio around dermatology, urology, respiratory, GI, and CV depending on the territory.

"We are pleased to receive this upfront and milestone payment of $2,200,000 from Gebro and look towards future potential milestone payments as we advance Piclidenoson through completion of our current Phase III trials in rheumatoid arthritis and psoriasis," stated Can-Fite CEO Dr. Pnina Fishman. Can-Fite recently initiated patient enrolment for its Phase III ACRobat trial of Piclidenoson for the treatment of rheumatoid arthritis.

The rheumatoid arthritis and psoriasis therapeutic market is dominated by biological drugs that are primarily administered via intravenous injection (IV) and have potential side effects. Rheumatoid arthritis and psoriasis are huge unmet need markets, where rheumatoid arthritis is estimated to reach $35B in 2020 and psoriasis is forecast to reach $9B in 2018.

On January 25, 2018 Trovagene, Inc. (NASDAQ: TROV), a clinical-stage precision medicine biotechnology company, engaged in the development of targeted cancer therapies, reported the initiation of its Phase 2 clinical trial, evaluating the combination of PCM-075 and abiraterone acetate (Zytiga – Johnson & Johnson), in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) (Press release, Trovagene, JAN 25, 2018, View Source [SID1234523575]). This clinical trial is called UNITE, "A Phase 2 Study to Understand the Novel Combination of PCM-075 and Abiraterone and the Opportunity to Improve Treatment and Extend Response in Patients with Metastatic Castration-Resistant Prostate Cancer." The study will enroll 25 patients with mCRPC who are showing early signs of disease progression while on abiraterone/prednisone therapy and will evaluate the proportion of patients achieving disease control after 12 weeks of study treatment.

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"Initiation of the UNITE trial in mCRPC marks an important milestone in the clinical development of PCM-075 and builds upon the promising data from our completed and published Phase 1 trial in metastatic solid tumor cancers, as well as preclinical data demonstrating significant synergy for the combination of PCM-075 and abiraterone in CRPC tumor cells," said Bill Welch, Chief Executive Officer of Trovagene. "We are excited to be working with leading prostate cancer specialists and the Harvard Medical Institutions to conduct this trial and believe that the highly synergistic combination of PCM-075 and Zytiga has the potential to address the medical need to extend the benefit of response to treatment in patients with mCRPC."

Trovagene filed its Phase 2 metastatic Castration-Resistant Prostate Cancer protocol to the FDA and its active solid tumor IND in December, 2017. The Company successfully passed the 30-day FDA review period and has selected PRA Health Sciences as the Clinical Research Organization (CRO) to facilitate the trial.

About the Phase 2 mCRPC Clinical Study

In the UNITE multi-center, open-label, Phase 2 trial, the combination of PCM-075 with the standard dose of abiraterone and prednisone, all administered orally, will be evaluated to determine the proportion of patients achieving disease control after 12 weeks of study treatment. Disease control is defined by the lack of Prostate Specific Antigen (PSA) progression in patients who are showing signs of early progressive disease (rise in PSA, but minimally symptomatic or asymptomatic) while currently receiving androgen deprivation therapy (ADT) plus abiraterone and prednisone.

The Phase 2 UNITE trial will enroll 25 patients with metastatic Castration-Resistant Prostate Cancer showing signs of disease progression demonstrated by two rising PSA values separated by at least one week, while on abiraterone/prednisone therapy. The follow-up of patients will occur approximately every six weeks until disease progression in patients with stable disease, or better at the end of treatment assessments.

The Phase 2 trial also includes the following secondary observation endpoints:

The effects of PCM-075 in combination with abiraterone and prednisone on time to PSA progression in subjects with mCRPC;
The effects of PCM-075 in combination with abiraterone and prednisone on time to radiographic progression, based on the Prostate Cancer Working Group 3 (PCWG3) guidelines; and
The effects of PCM-075 in combination with abiraterone and prednisone on radiographic response (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) in subjects with mCRPC and measurable disease.
About PCM-075

PCM-075 is a highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple hematologic and solid tumor cancers. Studies have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates up to 31% were observed when used in conjunction with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of PCM-075 has been completed in patients with advanced metastatic solid tumor cancers, and published in Investigational New Drugs.

PCM-075 only targets PLK1 isoform (not PLK2 or PLK3), is oral, has a 24-hour drug half-life with reversible on-target hematologic toxicities. Trovagene believes that targeting only PLK1 with reversible on-target activity and an improved dose/scheduling protocol can significantly improve on the long-term outcome observed in previous studies with a PLK inhibitor in AML.

PCM-075 has demonstrated synergy in preclinical studies with over 10 chemotherapeutic and target agents used in hematologic and solid tumor cancers, including Zytiga (abiraterone), FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK-1 inhibitor, PCM-075, with other compounds has the potential for improved clinical efficacy in Castration-Resistant Prostate Cancer (CRPC), Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC) and Adrenocortical Carcinoma (ACC).

About Castration-Resistant Prostate Cancer (CRPC)

Castration-Resistant Prostate Cancer (CRPC) is defined by disease progression despite androgen-deprivation therapy (ADT) and may present as one or any combination of a continuous rise in serum levels of prostate-specific antigen (PSA), progression of pre-existing disease, or appearance of new metastases. Prognosis is associated with several factors, including performance status, presence of bone pain, extent of disease on bone scan, and serum levels of alkaline phosphatase. Bone metastases occur in 90% of men with CPRC and can produce significant morbidity, including pain, pathologic fractures, spinal cord compression, and bone marrow failure. Paraneoplastic effects are also common, including anemia, weight loss, fatigue, hypercoagulability, and increased susceptibility to infection. Institution of treatment and the choice of systemic or local therapy depend on a number of factors.