First Patient Dosed in IST of CDK Inhibitor Seliciclib in Cushing’s Disease, a Serious Endocrine Disorder

Source:Cyclacel Pharmaceuticals, Inc.

BERKELEY HEIGHTS, N.J., July 2, 2015 (GLOBE NEWSWIRE) — Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP) (Cyclacel or the Company), a biopharmaceutical company developing oral therapies that target the various phases of cell cycle control for the treatment of cancer and other serious disorders today announced that the first patient has been dosed in an investigator sponsored trial (IST) of the Company’s oral cyclin dependent kinase (CDK) inhibitor seliciclib in Cushing’s disease (CD)1. Clinicians at Cedars-Sinai, Los Angeles, were awarded a grant from The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to evaluate seliciclib, a CDK2/9 inhibitor currently in clinical development to treat certain cancers, as a potential therapy for CD.

“Cushing’s disease is a serious debilitating endocrine disorder with limited treatment options for patients,” said Shlomo Melmed, M.D., Director of the Burns and Allen Research Institute, Principal Investigator and Dean of the Medical Faculty at Cedars-Sinai, Los Angeles. “We believe that seliciclib is unique among clinical stage CDK inhibitors in its potential effectiveness to treat this disease. Its mechanism of action has a dual effect as it impacts tumor growth by decreasing the levels and activity of cyclin E, as well as inhibiting ACTH production. If our trial with seliciclib proves successful, it could lead to dramatically improved treatment outcomes for patients with Cushing’s disease.”

CD is an endocrine disorder caused by adrenocorticotropin (ACTH)-producing pituitary tumors, often leading to obesity, diabetes, hypertension, osteoporosis and increased risk of death if inadequately controlled. Cell cycle dysregulation is a common feature of pituitary tumors, including upregulation of cyclin E, specifically seen in tumors of the corticotroph lineage, such as in CD. Dr. Melmed and Dr. Ning-Ai Liu have previously published preclinical proof-of-concept data showing that seliciclib is uniquely effective amongst CDK inhibitors in resolving the disease, with dual effects on pituitary growth and ACTH production2.

The trial is a Phase 2 proof-of-concept, open-label, single arm study to assess the safety and efficacy of seliciclib in CD. Sixteen patients with de novo, persistent or recurrent CD will receive seliciclib for 4 weeks prior to standard-of-care treatment. The primary objective is to establish the efficacy of seliciclib on normalizing urinary free cortisol levels in patients with CD.

About Cushing’s disease

CD is a rare endocrine, orphan disorder with estimated US prevalence of approximately 20,000. It is the most common cause of endogenous hypercortisolism, which predisposes patients to central obesity, diabetes, hypertension, osteoporosis and substantially increases their risk of infection, thrombosis and psychiatric disorders. If inadequately controlled, CD is fatal with mortality rate four-fold-higher than that of age- and sex-matched controls and median survival of 4.6 years. The leading cause of death in CD is cardiovascular disease. CD remains an unmet medical need despite available therapies.

About seliciclib and its mechanism of action in Cushing’s disease

Seliciclib, an orally-available CDK2/9 inhibitor, has been evaluated to date in approximately 450 patients and is currently being explored in combination with Cyclacel’s orally-available sapacitabine in patients with solid tumors.

Seliciclib has been shown in preclinical models to be uniquely effective amongst other CDK inhibitors. Seliciclib was subsequently shown, in mouse corticotroph tumor cells in vitro, to cause cell cycle arrest, accompanied by decreases in cyclin E levels, increased p27Kip1, p57Kip2 and p21Cip1 expression, and reduced Thr821 phosphorylation of the retinoblastoma (Rb) protein. Rb is reportedly a site phosphorylated by CDK2. In addition, ACTH concentrations in cell supernatant were also decreased by seliciclib, suggesting a dual impact of the compound on corticotroph tumorigenesis. In vivo, oral administration of seliciclib led to a 50% reduction in tumor weight, and consistent with in vitro observations, reduced plasma ACTH levels, serum cortisol levels and tumor PCNA staining.

1. ClinicalTrials.gov (NCT02160730).

2. Liu, N-A., Jiang, H., Ben-Shlomo, A., Wawrowsky, K. Fan, X-M., Lin, S. and Melmed, S. (2011) Targeting zebrafish and murine pituitary corticotroph tumours with a cyclin-dependent kinase (CDK) inhibitor. PNAS doi: 10.1073/pnas.1018091108

About Cyclacel Pharmaceuticals, Inc.

Cyclacel is a biopharmaceutical company developing oral therapies that target the various phases of cell cycle control for the treatment of cancer and other serious diseases. Sapacitabine, Cyclacel’s most advanced product candidate, is the subject of SEAMLESS, a Phase 3 trial, which has completed enrollment and is being conducted under an SPA with the FDA as front-line treatment for acute myeloid leukemia (AML) in the elderly, and other indications including myelodysplastic syndromes (MDS). Cyclacel’s pipeline includes an oral regimen of seliciclib in combination with sapacitabine in a Phase 1 study of patients with Homologous Recombination (HR) repair-deficient breast, ovarian and pancreatic cancers, including gBRCA positive tumors, and CYC065, a novel CDK2/9 inhibitor, with potential utility in both hematological malignancies and solid tumors. Cyclacel’s strategy is to build a diversified biopharmaceutical business focused in hematology and oncology based on a development pipeline of novel drug candidates. Please visit www.cyclacel.com for more information.

Forward-looking Statements

This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and intended utilization of Cyclacel’s product candidates, the conduct and results of future clinical trials, plans regarding regulatory filings, future research and clinical trials and plans regarding partnering activities. Factors that may cause actual results to differ materially include the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, trials may have difficulty enrolling, Cyclacel may not obtain approval to market its product candidates, the risks associated with reliance on outside financing to meet capital requirements, and the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “forecast,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company’s most recent Annual Report on Form 10-K and other periodic and other filings Cyclacel files with the Securities and Exchange Commission and are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Cyclacel assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

© Copyright 2015 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.

Cyclacel Pharmaceuticals, Inc.

Company:
Paul McBarron, (908) 517-7330, 
Investor Relations:
Russo Partners LLC, Robert Flamm, (212) 845-4226

– See more at: http://globenewswire.com/news-release/2015/07/02/749361/10140470/en/First-Patient-Dosed-in-IST-of-CDK-Inhibitor-Seliciclib-in-Cushing-s-Disease-a-Serious-Endocrine-Disorder.html#sthash.KgdD65N9.dpuf

RARE Patient Advocacy Summit Details and Invitation

We would like to invite you and your community to join us for our fourth annual RARE Patient Advocacy Summit September 24 – 25, 2015 in Huntington Beach, California!  Join the community at this unique event for rare disease patients and advocates: Connect. Educate. Engage. Achieve. 

Registration is open!

This Summit is for every patient, patient advocacy leader, and anyone who cares about rare.  Please take a look at this year’s compelling agenda and consider participating in an event that you won’t want to miss!

 

Why attend? Here’s what you’ll gain:

  • Practical next steps for taking action in the areas of research, legislation, fundraising, and community support
  • Core fundamentals and skills to help you start, grow and strengthen your nonprofit organization
  • Strategies for building online communities and why they are essential for rare disease awareness
  • Understanding the power of genetic data and patient involvement for advancing research for your disease
  • Tools and insights into crafting successful collaborations with researchers, biotech, pharma and the FDA
  • Invaluable connections with advocacy leaders that will help you define and propel your rare disease priorities forward

Register for the Summit and learn more on travel scholarships

Register now and secure your spot at the leading conference for rare disease patient advocates today!  We have a limited number of travel scholarships available, which you may request here.  Scholarship applications will be accepted through July 27, 2015.

 

Want to learn more?  Sign up for our Information Session!

Sign up today for an information session on the Summit where we’ll walk you through the details, the agenda and opportunities to learn and connect, and more on how to share this with your community. Here’s how to register for the information session on July 15, 2015 at 2:00 p.m. PDT/5:00 p.m. EDT. Patients, advocates, advocacy group leaders – all are welcome to participate!

 

Can’t attend in person?

There is no reason you, your organizational leadership or community should miss out!  Sign up to join the conference via Livestream through your computer and learn more about how you can still be an active participant using Twitter.

 

We hope to see you at the Summit!

 

Sincerely,

Kym, Carrie & Lisa

 

Kym H. Kilbourne                                          

VP, Patient Advocacy                                     

kymk@globalgenes.org

 

Carrie Ostrea

Manager, Advocacy/Parent Advocate

carrieo@globalgenes.org

 

Lisa Schill

Advocacy Ambassador/Parent Advocate

lschill@globalgenes.org 

Myth: “Vitamins and Natural Remedies can cure/heal Cushing’s”

myth-busted

 

More from Dr. Karen Thames:

Myth: “Vitamins and Natural Remedies can cure/heal Cushing’s”

Fact: Do you know how many people have told me that if I just “juice”, I will be cured from Cushing’s or Adrenal Insufficiency?! I appreciate the sentiment, but the sad reality is that no amount of juicing and no vitamin will cure Cushing’s. Some Cushing’s patients do take vitamins, some do eat raw food or paleo diets, and some even juice. However, this is just a lifestyle choice and not an attempt to cure Cushing’s. I must admit that when you have such a dreadful disease, you do sometimes take desperate measures to heal yourself. Perhaps, doing acupuncture or some other form of natural healing technique seems attractive at times. Take it from a person who has had acupuncture, seen many natural doctors, juiced, took vitamins, ate a raw food diet, and yes, I EVEN did a series of colonics! If you have ever had colonics, you know that it brings new meaning to the phrase, “no pain, no gain!”

Seriously, this is all before I knew I had Cushing’s. I watched as every person who administered the different kinds of treatment scratched their heads as I continued to gain weight, eventually at a rate of 5 pounds per week! They couldn’t believe that I was actually still gaining weight. Their natural and not surprising response, of course, was to project blame onto me. “Karen, there is NO way you are following protocol! You MUST be lying on your food log!” What we all didn’t realize is that I was suffering from a life-threatening illness called Cushing’s Disease that caused morbid obesity in me and that none of those “remedies” would EVER work!

Now, I have already been in Twitter wars over this topic. Someone tried to tell me that a raw food diet will “cure Cushing’s” and then she told me that I am “ignorant and in denial”! She proceeded to tell me that her daughter, though she had surgery to treat Cushing’s, was REALLY cured because of changing her diet. She also told me that the daughter, who had her Adrenal Glands removed, didn’t need steroids. Listen folks, this is VERY dangerous! I have no adrenal glands and I NEED steroids! Cortisol is life sustaining and you will die without it! I fully expect that someone will argue this point until the cows come home. It doesn’t matter. It won’t change the facts. Cushing’s is caused by excess cortisol in the body. The ONLY treatment is to target the source of the excess cortisol (i.e.brain tumor, adrenal tumor, ectopic tumor, or prolonged steroid use for another disease). Targeting the source is the first line of treatment. Cushing’s Syndrome/Disease will lead to death if not treated properly! #BattlegroundDiagnosis

Disclaimer: I am not a medical doctor. Please seek the advice of a medical professional if you have questions or need further assistance.

If you want to follow our documentary, please go to http://www.Facebook.com/Hug.A.Cushie

ALD403 (migraine drug) and ALD1613 (for Cushing’s disease)

As it moves into crucial Phase 3 drug trials for its flagship migraine treatment, Bothell-based Alder Biopharmaceuticals (Nasdaq: ALDR) is looking to raise a lot of cash.

Alder is offering up to $200 million shares of its common stock, according to SEC filings.

The company plans to use the money to develop its drugs ALD403 (its migraine drug) and ALD1613 (for Cushing’s disease), conduct clinical trials and commercialize these drugs. Funds will also go toward “general corporate purposes,” which might include the acquisition or licensing of other products, businesses or technologies, according to those filings.

From http://www.bizjournals.com/seattle/blog/health-care-inc/2015/06/alder-biopharmaceuticals-sets-out-to-raise-200m-to.html

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