Glactone Pharma: STAT3 interacts with the androgen receptor and is a drug target in enzalutamide resistant prostate cancer

In collaboration with researchers at Vancouver Prostate Centre in Canada, Glactone Pharma has discovered a novel way of enhancing the effects of current prostate cancer treatments. The research, published in the scientific journal Scientific Reports, demonstrates that STAT3 inhibition could be a part of a combination therapy together with anti-androgens against castration resistant prostate cancer thereby offering new treatment options for prostate cancer patients.

Prostate cancer is the most common form of non-cutaneous cancer in men. The yearly incidence in the seven largest markets is over 400,000 men and the number of patients exceeds 1,6 million. In many cases the disease progresses to a state were androgen deprivation no longer has any effect, so called castration resistant prostate cancer (CRPC). However, primary and acquired resistance to current drugs is a very large clinical problem and treatments that either reverse or prevent resistance would have a great impact on the treatment of prostate cancer. Metastatic CRPC is almost always incurable.

Glactone Pharma is a Swedish biotech company developing novel drugs that can inhibit the transcription factor STAT3, a highly relevant drug target in cancer, including prostate cancer. Using the natural product galiellalactone as a starting point, Glactone Pharma has built a unique and promising portfolio of STAT3 inhibitors with excellent druglike properties that can address unmet medical needs. Together with the company’s innovators at Lund University and other academic collaborators, Glactone Pharma has built a strong scientific case that STAT3 is an important target in prostate cancer.

Together with a research group at the Vancouver Prostate Centre in Canada, it has now been shown that STAT3 can interact with the androgen receptor (AR) and enhance the AR signaling that drives prostate cancer. Furthermore, treating prostate cancer cells with a clinically used anti-androgen drug, enzalutamide, resulted in STAT3 activation. Finally, enzalutamide resistant prostate cancer cells became sensitive to STAT3 inhibition using the natural product galiellalactone. In conclusion the results show that targeting STAT3 has the potential to stop or reverse treatment resistance, prevent disease progression and enhance the effect of current drugs used in prostate cancer. The results have been published as an article, “Galiellalactone inhibits the STAT3/AR signaling axis and suppresses Enzalutamide-resistant Prostate Cancer”, in Scientific Reports, a scientific journal from the publishers of Nature.

Martin Johansson, CEO of Glactone Pharma, says: “Based on these new findings, we believe we can address a great unmet medical need and potentially bring forward innovative and effective treatment options for prostate cancer patients. We are very grateful for this productive collaboration with the Vancouver Prostate Centre.”

About STAT3
STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor/signaling protein that is frequently activated in many forms of cancer.

STAT3 is a highly promising target in cancer with both preclinical and clinical data supporting the important roles that STAT3 plays in cancer occurrence and progression. In particular, STAT3 is involved in mechanisms that enable tumors and cancer cells to escape the immune system and also become treatment resistant.

STAT3 is an intractable drug target as it is an intracellular protein with no enzymatic activity and is activated by multiple upstream factors. Despite STAT3 not being a “classic drug target”, Glactone Pharma has developed orally bioavailable small molecule inhibitors that can directly inhibit the function of STAT3.

Link to the on-line article “Galiellalactone inhibits the STAT3/AR signaling axis and suppresses Enzalutamide-resistant Prostate Cancer”:
https://www.nature.com/articles/s41598-018-35612-z.

About Glactone Pharma
Glactone Pharma is a biotech company within PULS and is based on ground-breaking science from Lund University in Sweden. PULS is a Swedish life science company with a unique combination of scientists and industrialists who together with innovators are commercializing ideas by providing capital, know-how and committed partnership.
Glactone Pharma has developed a pipeline of novel potential drugs that target the STAT3 transcription factor for the use in immuno-oncology and for the treatment of advanced treatment resistant cancers. STAT3 is directly involved in tumor mediated immune suppression and in treatment resistance making it an ideal target in combination treatments.
To read more, visit www.glactone.com and www.pulsinvest.se.

For more information, please contact
Jan Törnell, Chairman of the Board, Glactone Pharma AB, +46 (0)70 676 00 08 or jan.tornell@pulsinvest.se
Martin Johansson, CEO, Glactone Pharma AB, +46 (0)76 006 60 29 or martin.johansson@glactone.com

Oncorena raises SEK 14.5 million to prepare for clinical study in advanced kidney cancer

Oncorena Holding AB today announces that the company through a share issue has raised capital to build its organization and resources in preparation for clinical development with a patient study of a new treatment modality for advanced kidney (renal) cancer. The capital was raised from Oncorena’s largest shareholders P.U.L.S. AB and HealthCap, as well as other current shareholders. In addition, several new investors have made significant investments.

The new capital will be used to build the company’s organization and resources, as well as all activities needed in preparation for the planned clinical study. In the phase I-IIa study to be conducted in patients with advanced kidney cancer on dialysis will be treated with Oncorena’s potential new drug orellanine. Orellanine is a substance that is taken up specifically by kidney cancer cells and kidney cells, pre-clinical experimental studies have shown very promising results.

“The new capital provides an important infusion to enable necessary steps in the development of orellanine into a novel treatment for patients with advanced renal cancer. The medical need is high for these patients since there is no effective treatment with good tolerability available today,” says Lars Grundemar, CEO of Oncorena.

“It will be a strategically important step for Oncorena when the clinical patient study with this innovative compound can be started. I am therefore pleased to notice the great confidence in Oncorena amongst the existing shareholders as well as from new investors,” says Bengt-Åke Bengtsson, chairman of Oncorena’s board.

For further information, please contact
Lars Grundemar, CEO, Oncorena Holding AB, lars.grundemar@oncorena.com,
phone +46 (0)76 209 5518
Bengt-Åke Bengtsson, Chairman of the Board, Oncorena Holding AB, bengt-ake.bengtsson@medic.gu.se, phone +46 (0)70 746 0000

About kidney cancer
Approximately 1 in 10,000 is afflicted with kidney cancer annually. 80% of the patients are between 40 and 69 years of age when they are diagnosed (median age 63 years). The disease can often be cured with surgery if detected in time, but unfortunately the diagnosis is often made when the tumor has already spread to other organs. The prognosis is then considerably less favorable and certain groups have a median survival of only approx. 1.5 years. Today the disease is treated with various types of drugs, often with severe side effects, and standard chemotherapy drugs have only limited effect. There is therefore a high need for new, effective and safe drugs.

About Oncorena
Oncorena develops a completely new and potentially revolutionizing treatment for patients with metastatic kidney cancer. The treatment is based on research from the University of Gothenburg in Sweden led by Professors Börje Haraldsson and Jenny Nyström. The project was initially developed with support from Vinnova (Sweden’s Innovation Agency) and GU Ventures in Sweden. Oncorena is a part of the P.U.L.S. AB’s portfolio since 2013 and also part of HealthCap´s portfolio since 2016.  Learn more at www.oncorena.com.

About orellanine
The substance, orellanine, originally emanates from a mushroom and has been inadvertently ingested by a number of people. The clinical effects are well documented and are limited to the kidneys. As the target group for the treatment is patients with metastatic kidney cancer who are undergoing dialysis, the side effect profile is believed to be relatively mild. Experimental studies indicate that the effect may be dramatically positive.

About PULS
PULS (Partners for Development Investments in Life Sciences, P.U.L.S. AB) is a Swedish life science company with a unique combination of researchers and industry representatives who work together with innovators to commercialize ideas through capital, know-how and a committed partnership. PULS invests in early projects and develops them in close collaboration with innovators, shepherding them all the way from idea to completed attractive project for industry. Since 2002 PULS has started eleven project companies: two were sold, one was discontinued, two were floated on the stock market (AcuCort and LIDDS), and one was outlicensed (Laccure). PULS has its headquarters in Helsingborg. Current PULS projects: Adenovir Pharma, Belina, Glactone Pharma, Oncorena and Trophea. www.pulsinvest.se.

About HealthCap
HealthCap is a European venture capital firm investing exclusively and globally in life sciences. The investment strategy focuses on diseases with high unmet medical needs and breakthrough therapies that have the potential to be transformative and change medical practice, and the lives of patients suffering these conditions.
Having raised more than EUR 1 billion since 1996, HealthCap has backed and built more than 100 companies, taken more than 40 companies public and done numerous trade sales.
Over the years, HealthCap companies have developed more than 20 pharmaceutical products to market approval, many of which are breakthrough therapies helping patients with life-threatening diseases. www.healthcap.eu

Trophea’s topical combination product against skin atrophy progresses into clinical Phase I

The Danish Medicines Agency and the Ethics Committee in Region Sjaelland have both given Trophea Development approval to initiate the first clinical study, a Phase I study, with an innovative combination product against skin atrophy. The clinical study will be performed at Sjaelland’s University Hospital in Roskilde in Denmark.

The development program has progressed according to plan. Trophea’s topical combination product has been developed and manufactured according to Good Manufacturing Practice (GMP), the preclinical phase has been completed and the project is now progressing into the clinical phase. The project is based on an innovative combination of two well-documented and studied substances with different mode of actions of which both seem to reverse skin atrophy.

A recognized problem in connection with long-term treatment with corticosteroids is that patients may develop skin atrophy as a side-effect. The innovator group has shown that a combination of two well-known substances increases the formation of procollagen in the skin, promoting the regeneration of the damaged atrophied skin.

“A product that effectively can treat skin atrophy is highly asked for since there are no such treatments today. People that are at risk for developing skin atrophy, and may be helped by this new treatment, would be psoriasis, atopic dermatitis and eczema patients with long time exposure to glucocorticoids,” says Jan Faergemann, innovator and Professor in Dermatology at Sahlgrenska Academy, University of Gothenburg in Sweden.

“I am very pleased that our development program has reached this important milestone enabling us to initiate the company’s first clinical trial with Trophea topical combination gel against skin atrophy,” says Jeanette Robertsson, project leader at Trophea Development AB.

About Trophea
Trophea is a start-up company developing an innovative medication against skin atrophy. Trophea AB and its subsidiary Trophea Development AB were founded in 2016. The companies are part of the group of the Swedish company PULS (Partners for Development Investments in Life Sciences, P.U.L.S. AB) and are based in Helsingborg, Sweden. For further information about Trophea and the project, see www.tropheadevelopment.com.

About PULS
PULS (Partners for Development Investments in Life Sciences, P.U.L.S. AB) is a Swedish life science company with a unique combination of researchers and industry representatives who work together with innovators to commercialize ideas through capital, know-how and a committed partnership. PULS invests in early projects and develops them in close collaboration with innovators, shepherding them all the way from idea to completed attractive project for industry. Since 2002 PULS has started eleven project companies: two were sold, one was discontinued, two were floated on the stock market (AcuCort and LIDDS), and one was outlicensed. PULS has its headquarters in Helsingborg. Current PULS projects: Adenovir Pharma, Belina, Glactone Pharma, Oncorena and Trophea. www.pulsinvest.se.