The explosion of new biotechnologies and access and understanding of newly mined genomic information has spurred biotech companies and researchers into developing new therapies for age-old diseases as well as searching for ways to combat the aging process and actually extend human life. Alkahest, based in San Carlos, Calif., is one of those pioneering companies concentrating on a new approach to find the “fountain of youth.”
Alkahest researchers are developing therapies derived from blood and its components with a focus to improve vitality and function into old age. The company is working on treatments for diseases of aging, with an emphasis on cognitive dysfunction and dementia, which are key medical challenges. The company’s pioneering research has demonstrated that factors in young plasma are able to reverse brain deficits in preclinical models relevant to normal aging and Alzheimer’s disease. Conversely, an inhibition of factors that are present in old plasma can improve brain functions in preclinical models of age-related cognitive decline. The company is conducting clinical studies in patients with different types of dementia and other neurodegenerative diseases.
Joseph McCracken is Alkahest’s vice president of Business Development. He was previously vice president and global head of Business Development & Licensing for Roche Pharma, where he was responsible for Roche Pharma’s global in-licensing and out-licensing activities. Prior to joining Roche Pharma, McCracken held the position of vice president, Business Development at Genentech for more than 10 years, and has also held similar positions at Aventis Pharma and Rhone-Poulenc Rorer.
WuXi AppTec Communications, as part of a new industry series, recently interviewed McCracken about the clinical direction and goals of Alkahest as well as what the future holds for research into extending human life.
WuXi: How do you define aging? Is it an illness itself? Is it a specific group of diseases?
Joseph McCracken: There are many different contextual definitions of aging. A popular definition has been offered by Michael Rose, who has described aging as “a decline or loss of adaptation with increasing chronological age, caused by a time-progressive decline of Hamilton’s forces of natural selection.” Aging itself not generally considered an illness, although aging is a risk factor of a number of age-related illnesses.
WuXi: What is your anti-aging technology and how are you applying it?
Joseph McCracken: Alkahest does not have a single “anti-aging technology.” The company is developing novel treatments for age-related diseases in order to extend the span of healthy living, and the company’s discovery engine is based on understanding changes in the plasma proteome in healthy aging and in age-related diseases. Circulating plasma, which connects the brain and other organs, contains thousands of proteins that “signal” or mediate biological processes in healthy aging and in age-related diseases. Those proteins that increase in age-related diseases, or negative chronokines, are targets for inhibition; while those proteins that decrease in age-related diseases, or positive chronokines, are targets for replacement or augmentation.
WuXi: What is the goal of your technology? Is it improving quality of life for more years or extending the average life span?
Joseph McCracken: Our mission and goal as a company is to extend the span of healthy living by developing novel treatments for age-related diseases. If we can develop products that improve the quality of life for patients with neurodegenerative or other diseases of aging, we will have succeeded in our mission.
WuXi: How does your approach differ from other companies in this field?
Joseph McCracken: Our approach to discovering and developing new therapeutic modalities is based on our unique insights into changes in the plasma proteome in healthy aging and age-related diseases. We are focused on systemic organismal aging instead of cell-autonomous aging. Also, our approach to treating Alzheimer’s disease is unbiased and multifactorial, as opposed to approaches that rely on a single pathway or target. ALK6019, which we are evaluating for the treatment of Alzheimer’s disease, is a proprietary plasma fraction that contains a number of proteins and has been shown to stimulate neurogenesis and enhance cognition in animals. We do not believe the use of whole plasma represents a practical approach to the treatment of neurodegenerative diseases, and we are focused on developing novel plasma fractions that are regenerative, while overcoming the many medical and practical limitations of whole plasma.
WuXi: How will anti-aging strategies evolve over the next five to 10 years?
Joseph McCracken: I believe there will be more focus on the plasma proteome which will be enabled by better technologies, better sample reliability, better clinical annotation and better techniques for data analysis. Looking further ahead, understanding changes in the metabolome will become more important.
WuXi: Do you need a different business model than a traditional biotech or pharma company? If so, what are the differences?
Joseph McCracken: We don’t need a radically different business model, but our long-term partnership with Grifols has enabled us to leverage their infrastructure and expertise in discovering, developing and manufacturing our plasma-derived products.
WuXi: What are the major challenges you face in developing and marketing your anti-aging technology?
Joseph McCracken: Anti-aging has become a very “noisy” field populated with pseudo-science and unsubstantiated claims. Unfortunately, the general media has often been unable or unwilling to separate serious scientific investigation from sensationalistic stories filled with unrealistic promises or fears.
WuXi: What kinds of collaborations are essential for your company?
Joseph McCracken: Our strategic alliance with Grifols, which enables us to leverage their infrastructure and expertise in plasma biology, has been critical to our success in building a unique technology platform. We also acquired a clinical stage small molecule that modulates one of our key targets for treating age-related diseases from a multinational pharmaceutical company, and we anticipate additional and similar alliances.
WuXi: What kinds of global partnerships do you have or plan to pursue?
Joseph McCracken: Our strategic alliance with Grifols is largely focused on the development, manufacturing and commercialization of our lead product, ALK6019 which will be in Phase 2 clinical trials in Alzheimer ’s disease and Parkinson’s in the first half of 2018, as well as other proprietary plasma derived products. We also acquired a clinical stage small molecule, ALK4290 which will be in a Phase 2 trial in age-related macular degeneration in the first half of 2018, from a multinational pharmaceutical company. Looking ahead, we anticipate additional alliances that accelerate the development of new treatments for age-related diseases, and we are currently in active discussions concerning such alliances.
WuXi: What challenges do you face in structuring clinical trials to evaluate your technology?
Joseph McCracken: Many of the neurodegenerative and other age-related diseases we are targeting are chronic diseases, which require long timelines to demonstrate efficacy. These trials are also very expensive, but we are confident that our existing and forthcoming data will enable us to raise the requisite funding from various sources.
WuXi: What regulatory challenges do you anticipate?
Joseph McCracken: We don’t really anticipate any unique regulatory challenges. To the contrary, we have found regulatory agencies to welcome our unique approach to the treatment of neurodegenerative disease, and especially in Alzheimer’s disease where the medical need is so great and where there has been such limited success in targeting beta-amyloid, and other single target pathways.
WuXi: How soon will an anti-aging medicine be available?
Joseph McCracken: We try not to predict timelines for the approval of novel therapeutic agents, but we will be initiating Phase 2 clinical studies with two novel products in the first half of this year.
WuXi: How will your anti-aging technology change medical care?
Joseph McCracken: The Alzheimer’s Association states that if you could delay the disabling symptoms of Alzheimer’s disease by five years, you would reduce the incidence of that disease by nearly 40%. That would certainly change medical care, and we believe it is a realistic goal for our clinical candidate, ALK6019. We are also developing an orally available small molecule for the treatment of Wet AMD. If successful, this could enable some patients to forego intravitreal injections and also help some patients in earlier stages of macular degeneration where intravitreal injections are not appropriate.
WuXi: What are the societal implications of extending the average life span by 10 or 20 years?
Joseph McCracken: If we can extend the time that individuals live a healthy life, we will be offering a tremendous benefit to individuals and society. If, for example, you could reduce or eliminate the time that patients are living in the memory-care units of nursing homes, this would have tremendous economic benefits to society.
WuXi: What technological advances do you expect to see in 2018 in your disease area?
Joseph McCracken: Better technologies for elucidating changes in the plasma proteome will offer new insights into the biology of neurodegenerative and other age-related diseases, and identify new targets for treatment of these diseases. This will be facilitated by better tools for data mining and interpretation. We will also see better technologies for disease diagnosis that will link patients to appropriate disease treatments.