Moleculin Biotech, Inc. is a pre-clinical and clinical-stage pharmaceutical company focused on the development of game-changing anti-cancer drug candidates, many of which are based on discoveries made at M.D. Anderson Cancer Center. Each of our projects represents a breakthrough discovery and a highly disruptive technology.

Annamycin: A New Hope For AML Patients

THE STATE OF ACUTE MYELOID LEUKEMIA TREATMENTS AND A LOOK AT CURRENT & FUTURE TREATMENT OPTIONS LIKE ANNAMYCIN
AML (Acute Myeloid Leukemia) is a lethal form of cancer that starts in the tissues that form blood and currently has only one first-line treatment option. Since there are no approved second-line therapies, if the patient fails first-line therapy, the chances of survival diminish greatly.

pieOf the 19,950 projected cases of AML in 2016, we estimate that on average:

• Only 20% of patients who receive first-line therapy will meet the requirements to qualify and receive a curative bone marrow transplant, the procedure that can provide remission and save lives. Bone marrow transplants greatly increase survival rates among the AML population, so the goal is to qualify for one.

• The remaining 80% (roughly 15,000 projected in 2016) will likely be dead within 6 months of treatment despite receiving the best option available called “7+3”. (A company called Celator Pharmaceuticals (CPXX) is changing this statistic with their own formulation called Vyxeos which we will discuss later on in this article.)

A PROBLEMATIC 50-YEAR-OLD TREATMENT

Most blood cells are developed in the bone marrow.

In a person who has developed AML, cancerous white blood cells are produced instead and cause the body’s circulatory system to fail.

The first-line treatment for eradication of these cancerous cells is called “7+3 induction therapy”, a 50+ year old treatment that we estimate is only effective for about 20% of the AML population.

This treatment consists of:

• 7 days of chemotherapy of a drug called Cytarabine and;
• 3 days of chemotherapy of a drug from the anthracycline family (the most commonly used anthracycline today is called daunorubicin)

In order to achieve remission and become eligible for a curative bone marrow transplant, the patient must post very positive results from the first-line (induction phase) therapy, which requires destruction of 95% of the leukemia cells.

On average, we estimate that around 80% of all AML patients will fail to respond or relapse from this highly toxic chemotherapy regimen called 7+3, for which the anthracyclines used possess two widely acknowledged flaws:

• They are highly cardiotoxic, which causes severe, permanent and sometimes fatal damage to the heart and;
• The cancer cells begin to recognize the anthracyclines as a foreign agent to the body and pump it out before the cancer can be killed. This is called “multidrug resistance”.

With every unsuccessful 7+3 induction therapy attempt, the patient’s ability to tolerate it and survive it drops. And, at the same time, the patient’s cancer cells build up more and more resistance to the drugs.

Without second-line treatment options, odds are, if a patient doesn’t achieve a complete response with the first-line therapy, they will likely die within 6 months.

A RECENT BREAKTHROUGH

celator_popup244x104In the last year, many people in the AML field have been watching a company named Celator Pharmaceuticals (NASDAQ: CPXX). Celator’s stock has greatly appreciated since the announcement of its Phase III clinical results and recently a large pharmaceutical company just announced its intention to acquire Celator for $1.5 billion.

All of this excitement has been the result of clinical findings demonstrating that by tweaking the delivery method of the existing “7+3 induction therapy”, for the 80% of patients that do not achieve a complete response, their expected lifespan will increase to 9.5 months versus a 6-month prognosis for the classical treatment.

Celator took the standard 7+3 formula and combined the two drugs into one liposomal formulation (at a 5:1 ratio). Administered in three IV injections over 5 days, patient lifespan was increased from 6 months to 9.5 months – an extra 3.5 months, an almost 50% increase in survival time. From a patient point of view, an extra 3.5 months of survival time is a gift. Importantly, an additional 9% of patients receiving Vyxeos went on to receive a bone marrow transplant as compared with 7+3.

If the FDA approves Vyxeos as a new first-line therapy, there is a good possibility that it could become the new standard of care for AML patients.

Based on the data available, although Vyxeos represents an important improvement in first-line therapy, it still leaves the vast majority of patients without a cure or a second-line option. It also doesn’t appear to tackle the fundamental problems attributed with currently approved anthracyclines: cardiotoxicity and multi-drug resistance.

TREATING THE UNLUCKY 80%

annamycinHope is on the way with our new lead drug candidate Annamycin. Developed with the world-renowned cancer institute MD Anderson, the world’s largest cancer research center, our drug candidate will soon be entering Phase IIb clinical trials.

Still classified as a member of the anthracycline family, it has been engineered to be non-cardiotoxic and “invisible” to the body’s natural defense mechanisms. Thus allowing it to not be recognized by the multidrug resistance pumps that plague current therapies.

You can watch an animation of how that works by clicking here.

Importantly, in animal tests used to evaluate cardiotoxicity, Annamycin has been shown to be non-cardiotoxic.

It’s important to note that cardiotoxicity is the number one dose limiting toxicity of currently approved anthracyclines used in the treatment of AML patients. Because of Annamycin’s lack of cardiotoxicity, patients will be able to be treated without the fear of life-threatening heart damage.

What’s most impressive about Annamycin, is that in the two most recent trials, Annamycin was able to generate significant activity with acute leukemia patients who would be considered part of the unlucky 80% or labeled as “untreatable.”

Specifically, in the most recent trial, 37% of patients who had failed an average of five previous induction therapies of 7+3, responded to Annamycin well enough to qualify for a curative bone marrow transplant. Putting this in the context of the recent Vyxeos data, that would be the equivalent of getting an additional 30% of patients to qualify for a bone marrow transplant. And, at the same time, avoiding the risk for heart damage associated with Vyxeos and the current standard of care.

The importance of this cannot be overstated, as we believe it makes Annamycin a potential game-changer in the treatment of AML patients.

Annamycin was given to a population of AML patients that didn’t respond to first-line therapy. On average, they received 5 induction therapies which ALL failed. Induction therapies like 7+3 are extremely aggressive treatments and take a significant toll on patients while trying to kill the cancer. At this point in the patient’s life, after 5 treatments, their bodies are beginning to fail them and death is near.

Annamycin was able to take 37% of that near-death population and achieve a strong enough response to qualify them for a curative bone marrow transplant. This is why we believe there is truly new hope when it comes to the treatment of relapsed or refractory AML patients.

WHY SECOND-LINE?

It is very important to understand our strategy to seek approval as a “second line” therapy.

This begins with recognizing that the FDA has the ability to grant accelerated approval on the basis of fewer and smaller clinical trials where a drug has the potential to fill a “significant unmet need.”

Since there is NO approved second-line therapy for the treatment of relapsed and refractory AML patients and since an average of 80% of AML patients fail the first-line therapies, we believe the unmet need for a second-line therapy is truly significant and that Annamycin could potentially fill that void.

At the same time, since such a large majority of patients fail the first-line therapies, we believe becoming the ONLY second-line therapy has potentially greater value than a first-line drug that is only successful in a minority of patients.

Finally, if we are able to get approved as a second-line therapy, we can then focus on generating the expanded data required to ultimately seek approval as a first-line therapy.

CONCLUSION

We applaud Wall Street’s positive response to Celator’s initial data because we believe the landscape for treatment of AML is changing and we are appreciative that this change is being noticed and encouraged.

With Celetor’s Vyxeos and our Annamycin, we believe that we both have the potential to improve treatment and outcome in an area of medicine that has been stagnate for over fifty years and which is in dire need of therapeutic innovation.

We are extremely excited to bring this new discovery to market and we believe it could present positive options for treatment, care, and life that were previously unavailable.

FURTHER READING

This white paper is written and edited to provide a basic understanding of current trends and issues in AML treatment and where Annamycin fits into that spectrum. For further, in-depth reading on the topic, we encourage you to click around our website to learn more.