With the current paradigm shift towards precision medicine and patient-centricity at the core of drug development, the future is looking bright for cancer treatments. Moving away from traditional and often highly toxic cancer therapeutics that cause collateral damage on the patient’s body, today’s oncology drug development is looking to mitigate both individual patient toxicity and economic costs, by driving to a situation where patients and their cancers may be able to co-exist for many years.
While the pandemic rages on across the globe, another crippling illness has been quietly surging in recent times. Cancer cases have been rising over the years, accounting for nearly 10 million deaths in 2020. The illness is also the leading cause of death globally, according to the World Health Organization.1
Reframe Needed for Current Therapies
The last century saw a gradual introduction of chemotherapeutic agents, with a new class of drugs or major discovery occurring at the rate of almost one every 20 years, along with small incremental gains in-between. The development of molecular biology has led to an explosion in our understanding of cancer and the body’s response to cancer. This, in turn, has led to significant innovation in the oncology research and development space with new drugs being rapidly introduced for selected sub-groups of cancers and a parallel increase in response rates and stable disease. Additionally, we see the emergence of drugs in the immune-oncology space to allow the body to reject cancer, as well as other cellular and gene therapies.
Unfortunately, a number of these therapies, while more effective than the older generation of medicines, are quite costly. Despite being one of the world’s largest health problems, cancer drug development can take an average of 10 to 12 years2 to complete. Costs are thus driven by, among other things, the cost to successfully develop the drug and get it to market, the cost of the failures that occur along the way, and the cost of capital to fund these efforts. These drug costs not only strain the governmental healthcare budget but place considerable pressure on individual and family budgets.
Apart from being costly, traditional courses of therapy, such as chemotherapy, can cause collateral damage to the patient’s body and overall wellbeing through the process of eliminating both normal and malignant cancer cells.
Innovations in Modern Oncology Drug Development
However, this may no longer be the future for cancer therapeutics with the current paradigm shift towards precision medicine and selective oncology research. Moving towards a more personalised approach to medicine, modern oncology drug development is looking to take advantage of molecule medicine and rational drug design, and match the right drugs to the right people. This will not only help enhance the effect of cancer treatment but also combat the incapacitating side effects of conventional therapies such as hair loss, nausea, and immunocompetence.
The largest and most critical paradigm shift has been the move away from thinking of cancer as a handful of homogenous diseases (e.g., breast cancer, lung cancer, etc.) to thinking of cancer as a large number of disease subsets, each with an individual and unique solution.
The therapy is then targeted at what defines each subset, taking advantage of molecule medicine and rational drug design. Put differently, the prior approach was akin to throwing spaghetti at the wall, hoping something sticks, and calling that our solution to that cancer. Also, we relied on toxic chemicals to achieve this end. That was the art of killing cancer cells just a little faster than killing the patient, a not very desirable state of affairs. The current paradigm is to understand the biology of cancer, which means we are slicing and dicing cancer into a thousand plus orphan indications. We now develop drugs rationally that engage the target in question and do not cause harm elsewhere.
Increasing Focus on Asia-Pacific Cancers
Meanwhile, 60 per cent of the world’s cancer cases come from Asia, with the number expected to grow to 14 million by 2030.3 However, there has traditionally been a lack of research and development of treatments for cancers with a higher prevalence in Asia.
A number of factors drive this disparity. Larger, often Western pharma companies, are unwilling to commit resources to developing drugs whose major market may be predominantly Asia for fear of being unable to recoup development expenditure through high pricing of their drugs. Even when drugs are developed for cancers seen more globally, they are often not registered or marketed in Asian countries. And when they are sold there, the price point is such as to place them beyond the reach of a majority of patients. This, sadly, has led to a disparity in therapeutic options for cancers, be they Asia prevalent or not.
Even with economic factors set aside, there has been a reluctance to bring certain drugs to Asian countries for the perception of working in an environment with weaker intellectual property protection and contract enforcement. This has led to the increasing disparity between where cancer patients are located and where the drugs are readily available.
On the other hand, major pharma companies of Asian origin are only now starting to climb up the value chain of drug development from generics to branded generics to innovative drug development.
To counter this challenge, we at AUM Biosciences are pioneering a shift in the traditional “west to east” model that de-prioritises the Asian market for drug development over the US and European markets, and relies on a “western” pricing structure, placing the medicine out of the reach of many who need it. Aided by a US$27 million Series A funding round,4 AUM Biosciences seeks to leverage the growing population in Asia, the existence and continued growth of first-class medical facilities and medical researchers, and the willingness of Asian patients to participate in clinical trials to rapidly conduct world-class research and development in Asia.
The development process is faster, consuming less of the patent life of the drugs in development, and therefore preserving value. This can, in turn, translate into drugs coming to market faster and at a lower cost, thus addressing the needs of the Asian population and also supporting the flow of innovation from Asia to the world.
Amid today’s rapid pace of scientific advancement heralded by the development of molecular biology, AUM Biosciences is also focusing on advancing work on efficacious and highly selective targeted therapeutics in oncology, with a pivot to Asia cancers, through a portfolio of various drugs at various stages of development.
Drugs in the pipeline are selected to address multiple cancer types, thereby giving multiple shots on goal and substantially de-risking the drug development process. AUM’s focus is on drugging what many would consider undruggable intracellular targets in cancer and to delay or overcome resistance cancer cells may develop to various therapies.
AUM001 is a selective translation inhibitor that has robust activity against a number of cancer types while resulting in minimal side effects. By acting at a critical chokepoint in the cellular machinery, the point where RNA is translated to protein, several critical signal pathways can be inhibited. This results in both direct interference with growth signals, thus targeting the untargetable. Additionally, there is significant immune-oncology activity, altering the tumour milieu and making cancer cells susceptible to immune recognition and attack. AUM001 is entering phase 2 studies.
AUM302, on the other hand, is a designer molecule that targets a key cancer pathway, PI3K, and two other related pathways that allow cancer cells to become resistant to PI3K inhibition (PIM, mTOR). The PI3K class of drugs have shown good activity in haematological malignancies. We are developing this molecule for solid tumours (which are the vast majority of cancers) and are seeing very exciting activity against a number of common and rare tumour types. The remaining pre-clinical studies to apply for an investigational new drug application (IND) are being completed and we expect to file for an IND shortly and get the drug into the clinic for several indications.
The approach AUM has taken with AUM302 of combining activity against a central pathway and its resistance mechanisms is a novel concept. Traditionally, one tries to achieve this by administering two or three different agents of the same type, each with one activity. That risks drug interactions and potentially additive side effects. Our approach is to make a single drug with multiple designer activities that will greatly impair its ability to become resistant and thus, kill the cancer cell. This results in a much more potent product. Also, the potency increase can allow us to reduce how much drug we have to give and so can also result in fewer side effects. We expect to see other companies adopt a similar approach going forward.
The Future of Cancer Treatment in Asia
While our greater understanding of cellular and immune pathways has led to many fundamental breakthroughs and new classes of active drugs, we will certainly be seeing greater segmentation of the cancer field, with an increasing trend towards defining cancers at a molecular level rather than at an anatomic level.
While this segmentation means that each group or sub-group of patients will be treated with medications unique to their needs, it should naturally lead to higher success rates. It makes a lot of sense to treat a sub-type of cancer with a drug that works for it, as opposed to taking that drug and giving it to a larger group, only some of whom have the target that leads to a response.
Cancer is well on its way to becoming a chronic disease. We would, of course, want to see cures. However, if we cannot have cures today, oncologists and their patients will readily accept that cancer will someday be managed like diabetes or hypertension. The long-term goal, of course, is to have targeted therapies for the multiplicity of changes that result in cancer. They should be as effective as antibiotics are for many bacterial illnesses or even the various anti-retroviral drugs for HIV disease.
Meanwhile, there is a clear need for both effective and affordable therapies for our cancer patients. The current Western model of developing effective but highly expensive therapies that meet the needs of a small segment of the cancer population is a recipe for economic disaster. The inequity of active drugs being available in a handful of countries while cancer patients, both in those countries and in the rest of the world, are dying because the medications are unaffordable is unconscionable. Asian countries, with their growing as well as ageing population, have seen a rapid rise in the number of cancer patients.
We need to develop and deliver effective medicines to these patients on their terms, at a manageable human and economic cost. The trend towards targeted therapies and precision medicines has seen a reduction in classical cytotoxic drug type side-effects to side-effects that are perhaps somewhat milder and easier to manage in the community. This, in turn, should lead to better compliance and the gradual conversion from a fast and painful killer to a chronic disease that can be managed for many years. [APBN]
About the Author
Dr Harish Dave is the Co-Founder & Chief Medical Officer of AUM Biosciences and is Board-certified in Internal Medicine, Medical Oncology and Hematology. He has more than 35 years of experience in basic science, academia and industry and has conducted over 100 studies with a focus on haematology, oncology, and transplantation. Dr Dave has also had extensive interactions with the FDA and submitted multiple IND’s. He has a lengthy publication record and has spoken extensively both nationally and internationally. Dr Dave also has experience in the finance sector.