EDO announces next milestone for tinostamustine (EDO-S101) as first-in-human solid tumor study begins

EDO announces next milestone for tinostamustine

BASEL, SWITZERLAND – 9 October 2017:

Mundipharma EDO GmbH (EDO) has begun a US Phase 1/2 clinical study for tinostamustine (EDO-S101) in patients with advanced solid tumors at Stanford University, Cedars Sinai Medical Center (Los Angeles) and The Mayo Clinic (Scottsdale). The news follows the announcement last year of the first-in-human study for tinostamustine in relapsed/refractory hematological malignancies.

The initial phase of the new study has been designed to determine the safety, tolerability, maximum dose and optimal dosing schedule of tinostamustine as a single agent in patients with solid tumors, who have progressed after at least one line of therapy and no other standard therapy with proven clinical benefit is available. It will also investigate the pharmacokinetic profile. The study will then expand to evaluate toxicity and response rates in selected relapsed/refractory solid tumors including: small cell lung cancer (SCLC); soft tissue sarcoma (STS) or non-KIT gastrointestinal stromal tumors (GIST); triple negative breast cancer (TNBC); and ovarian cancer.

Although an effective option for some cancer patients, traditional DNA-damaging therapies have certain limitations which can result in resistance, for example, a failure to gain access to the DNA strands to break them or an inability to counteract the DNA repair mechanisms within cancer cells.1

Tinostamustine (EDO-S101) is an AK-DACi (a first-in-class alkylating deacetylase inhibiting molecule) that, in preclinical studies, has been shown to improve access to the DNA strands within cancer cells, break them and counteract damage repair.2-4 Preclinical studies suggest that these complementary and simultaneous modes of action have the potential to overcome resistance.4,5

Preclinical experiments in solid tumors show that tinostamustine exhibits efficacy in most SCLC cell lines, including those that are resistant to doxorubicin.5,6 Activity has also been established in preclinical studies for STS, TNBC and ovarian cancer.6

Dr. Thomas Mehrling, CEO of EDO commented: “Following the initial Phase 1 study in hematological malignancies, I am delighted that EDO is now embarking on a further clinical trial in solid tumors. People with advanced solid tumors can become resistant to treatment and often have a relatively poor chance of survival. Breaking through resistance is essential if we are to continue to address unmet needs in oncology. This is a key step in the investigation of a first-in-class treatment, which we hope will prove a vital addition for patients with limited current options.”

For further information, please visit www.edoncology.com

For further information on Mundipharma’s network of independent associated companies, please visit www.mundipharma.com

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About the study

The primary objective of the Phase 1/2 multicenter, clinical trial is to assess the safety, tolerability, maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of tinostamustine as a single agent in patients with solid tumors who have progressed after at least one line of therapy and no other standard therapy with proven clinical benefit is available. MTD will be established for two administration schedules. The secondary objective will be to establish the pharmacokinetic (PK) profile of tinostamustine. There will be an exploratory objective to correlate the extent of gene expression changes in tumor samples with anti-tumor activity. The study will take place at Stanford University, Cedars Sinai Medical Center (Los Angeles) and The Mayo Clinic (Scottsdale).

In the second phase, the study will expand into selected solid tumor cohorts including: relapsed SCLC; relapsed STS or non-KIT GIST; relapsed/refractory TNBC; and relapsed/refractory ovarian cancer. The primary objective of Phase 2 will be to assess objective response rate (ORR) and clinical benefit rate (CBR). The secondary objectives will include safety, progression-free survival, overall survival, duration of response and PK profiles.

For further information about the study please visit: www.clinicaltrials.gov

About Solid Tumors

Patients with advanced stage SCLC have a low chance of survival (8% relative 5-year survival rate for Stage III and 2% for Stage IV).7

Approximately 16% of patients with STS have advanced stage (metastatic) disease. For these patients, the relative 5-year survival rate is 16%.8

TNBC tends to be more aggressive than other types of breast cancer, is more likely to spread beyond the breast and more likely to recur after treatment. Relative 5-year survival rates are lower for TNBC than for other types of breast cancer. TNBC is not a good candidate for hormonal therapy or HER2 targeting treatments.9

Ovarian cancer is the seventh most common cause of cancer-related deaths in women worldwide.10 Relative 5-year survival rates vary significantly depending on cancer stage. The outlook is worse for those with advanced ovarian cancer.11

References

  1. Cheung-Ong K, et al. DNA-Damaging Agents in Cancer Chemotherapy: Serendipity and Chemical Biology. Chemistry & Biology 2013;20:648-59.
  2. López-Iglesias AA. The Alkylating Histone Deacetylase Inhibitor Fusion Molecule Edo-S101 Displays Full Bi-Functional Properties in Preclinical Models of Hematological Malignancies. Blood 2014; 124: (21). https://ash.confex.com/ash/2014/webprogram/Paper72121.html
  3. López-Iglesias AA. preclinical antimyeloma activity of EDO-S101 (bendamustine-vorinostat fusion molecule) through DNA-damaging and HDACi effects. 15th International Myeloma Workshop. 23−26 September 2015. Rome, Italy.
  4. Di Filippi R, et al. The First-In-Class Alkylating Histone Deacetylase Inhibitor (HDACi) Fusion Molecule EDO-S101 Exerts Potent Preclinical Activity Against Tumor Cells of Hodgkin Lymphoma (HL) Including Bendamustine Resistant Clones. 57th Annual Meeting and Exposition of the American Society of Hematology (ASH), 6 December 2015.
  5. Yan S, Xu K, Lin J, et al. Synergistic inhibition of tumor growth and overcoming chemo-resistance by simultaneously targeting key components in DNA damage/repair, epigenetic, and putative cancer stem cell signaling pathways using novel dual-functional DNA-alkylating/HDAC inhibitor and tumor suppressor gene nanoparticles in lung cancer. Cancer Research 2012;72( Suppl 1): Abstract 2741.
  6. Mundipharma EDO GmbH Data on file.
    https://ash.confex.com/ash/2014/webprogram/Paper70113.html
  7. National Cancer Institute SEER Database (1988-2001). American Cancer Society website. Last accessed April 2017: https://www.cancer.org/cancer/small-cell-lung-cancer/detection-diagnosis-staging/survival-rates.html
  8. National Cancer Institute. American Cancer Society website: Last accessed April 2017: https://www.cancer.org/cancer/soft-tissue-sarcoma/detection-diagnosis-staging/survival-rates.html
  9. Breastcancer.org website. Last accessed April 2017: http://www.breastcancer.org/symptoms/diagnosis/trip_neg/behavior
  10. Jemal A, et al. Global Cancer Statistics. Ca Cancer J Clin 2011;61:69-90.
  11. National Cancer Institute SEER database (2004-2010). American Cancer Society website. Last accessed April 2017: https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html

Mundipharma and CellAct announce new deal for the worldwide development and commercialization of smart chemotherapy CAP7.1

Mundipharma and CellAct announce new deal

Cambridge, UK, 9 August 2017 – the Mundipharma network of independent associated companies announced today that it has acquired from CellAct the worldwide development, commercialization and manufacturing rights to CAP7.1.  CAP7.1 is a novel pro-drug of anticancer agent etoposide which is metabolized into an active form by enzymes in the gastrointestinal tract that are particularly active in tumor cells. This innovative drug, invented at Charité – Universitätsmedizin Berlin, Germany, enables the focused release of this chemotherapeutic agent into tumor cells in higher doses while maintaining a good safety and tolerability profile1. The treatment will be progressed through Phase III trials by EDO, a company with a worldwide network of clinical connections and expertise in developing cancer therapies.

Biliary tract cancer, including gallbladder tumors, is the second most common primary hepatobiliary cancer, after hepatocellular cancer.2 Estimates suggest there are almost 140,000 deaths each year from biliary tract cancer; a 22% increase since 19903. Despite the availability of surgery and chemotherapy options for early and locally advanced disease, patients are not able to access any indicated second line treatments.

In Phase II studies CAP7.1 showed efficacy in this difficult to treat patient population, with 56% of patients meeting the primary objective of disease control, including tumour shrinkages.1 CAP7.1 treated patients displayed an estimated one-year survival rate of 40%, which is approximately 20% higher compared with current standard of care.4

Under the collaboration, CellAct will receive a double digit upfront payment and milestone payments. EDO will advance CAP7.1 into Phase III clinical trials and reformulate the drug to enable manufacturing scale-up. CellAct and Charité University Hospital will also both receive sales-related income through tiered royalties and milestone payments.

Dr Thomas Mehrling, Chief Executive Officer, EDO, said: “We are thrilled to be taking this promising treatment into the next phase of clinical trials. By working with a network of experienced clinical partners, EDO enables efficient drug development and we believe this will be of benefit to accelerate the development a potentially life-changing treatment in this area of great unmet patient need.”

Paul Medeiros, Senior Vice President Corporate and Business Development, said: “At Mundipharma, discovering and developing novel medicines to treat underserved oncological diseases is a key strategic priority. Our alliance with CellAct adds an important new potential therapy to our oncology portfolio and builds on our expertise in smart chemotherapies.”

Nalân Utku, Chief Executive Officer, CellAct, said: “The proven expertise of Mundipharma in medicines development and their commercial capabilities will enable the potential for CAP7.1 to help patients in this underserved disease area.  This alliance will also provide a valuable exit for our investors Peppermint VC and NRW Bank who have been supporting this program for many years.”

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About the Mundipharma network

The Mundipharma global network of privately-owned independent associated companies was founded in 1956 by doctors, and now operates in over 120 countries worldwide. We are focused on developing business partnerships to identify and accelerate meaningful technology across an increasingly diverse portfolio of therapy areas including respiratory, oncology, pain, and biosimilars. Consistent with our entrepreneurial heritage, we like to think we see what others don’t by challenging conventional wisdom and asking different and challenging questions. By working in partnership with all our stakeholders, the Mundipharma network develops medicines that create value for patients, payers and wider healthcare systems.

For more information please visit: www.mundipharma.com

About EDO

EDO is a member of the Mundipharma network of independent associated companies.

EDO is focused on the preclinical and clinical development of treatments for cancer types where there are currently limited options for patients. The company collaborates with its worldwide network of clinical connections and experienced partners to develop competitively differentiated compounds successfully for a range of cancer types.

As a privately-funded company it can offer rapid decision making combined with commercial flexibility and excellent execution.  

References

  1. Ulrich-Frank Pape, Stefan Kasper, Marianne Sinn, Karel Caca, Jan Kuhlmann, Ulrich Keilholz, Arndt Vogel, and Nalan Utku. Randomized, multicenter phase II trial of CAP7.1 in patients with advanced biliary tract cancers. Journal of Clinical Oncology 2016; 34:4_suppl, 441-441
  2. Hennedige TP, Neo WT, Venkatesh SK. Imaging of malignancies of the biliary tract- an update. Cancer Imaging. 2014;14(1):14
  3. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385:117-71
  4. Mihalache F, Tantau M, Diaconu B, Acalovschi M. Survival and quality of life of cholangiocarcinoma patients: a prospective study over a 4 year period. J Gastrointestin Liver Dis. 2010 Sep;19(3):285-90.