Drug development which happens to be powered by AI, is going ahead and countering incentives from the Inflation Reduction Act and also making the small molecules all the more attractive in the intricate inflammatory & immunology disease spectrum. It is well to be noted that biologics have been quite a dominant treatment modality when it comes to chronic inflammation and immunology diseases for the 3 decades to say the least. Still, even though biologics continue to garner excitement as well as draw funds within this space, the fact is that the pendulum is shifting toward smaller molecules, all thanks to the AI gamut.
Though the application of AI towards small molecule discovery happens to be a sector-wide trend, for immunology and inflammatory diseases, this still happens to be comparatively new and also very exciting taking into account how biologics have gone on to dominate the spectrum to an extent that’s not witnessed in any other disease areas. With AI, the research is going ahead and opening novel kinds of chemistry and, at the same time identifying small molecules with selectivities that happen to be targeted, safety profiles as well as pharmacological properties which are very steep to achieve, thereby enabling a fresh gen of I&I therapeutics.
There are many companies which have gone on to recognize this pendulum swing hence seeking to bank on the opportunity to get a breakthrough oral I&I medications to the market.
Biologics Aren’t Unassailable
The fact is that biologics happen to have many advantages that go on to explain their worth and dominance in the I&I space – they have a high selectivity for their targets, decent safety profiles, as well as a predictable pharmacology in place. Apart from this, it is impossible to pinpoint a biologic for any sort of a extracellular target having high degree of success. This is indeed a startling concept which is pretty new since the time the first biologics were developed 30 years back.
In contrast to this, the small molecules which happen to have been the mainstays of therapeutic for several diseases, they are a failure in I&I. This is due to the fact that treatment of chronic autoimmune diseases goes onto impose very high safety benchmarks, yet there are small molecules which happen to have suboptimal pharmacological traits and also have a dearth of high target specificity thereby leading to off-target toxicities. Because of this lesser than 8% of the small molecules as well as 11% of autoimmune drugs that are in the midst of development go on to succeed in reaching the market, they face post-approval setbacks to the point that include withdrawals from the market.
It is well to be noted that biologics also happen to have their own set of disadvantages. Many of the therapies happen to be approved for very narrow patient profiles and the side effects of on-target immunosuppressive action that they give further go on to reduce the patient numbers who use them. The fact is that biologics have to be administered intravenously or subcutaneously in a hospital setting and the patients may as well be reluctant to get these therapies due to their invasive nature or the inconvenience that may be caused in the process.
Importantly, the therapies aren’t available to certain patients in some parts of the world because of cost, storage concerns and also transportation. Because of the help of AI, small molecule therapies when it comes to I&I diseases – they have the potential to go ahead and address such kinds of limitations to the biologics. One – because of their size, small molecules can go on to engage the intracellular targets like transcription elements which are indeed beyond biologics’ reach. All this goes on to open the possibility of interfering directly with the intracellular pathways which in a way, the large biologics cannot. Two- AI is going to be a key factor when it comes to elucidating the intricate pathological mechanisms underlying the I&I diseases, which can as well lead to small molecule therapies that are better targeted. It also happens to be much easier to combine two or more small molecules rather than combining two or more large biologics and these are he combos that might as well prove to be the inventions when it comes to patient care.
Lastly, small molecules therapies happen to be readily available to patients across the world due to the fact that they are in general, less costly to make and can be easily transported. While AI is useful when it comes to discovering novel biologics, it is very well suited to overcome the historical disadvantages of small molecules and at the same time exploring the new ones that go on to capture all the natural advantages which the small molecules happen to have when it comes to the treatment of I&I diseases.
AI happens to be accelerating the discovery of small molecules when it comes to I&I diseases
It is well to be noted that the first wave of AI platforms throughout the biopharma sector as well as numerous disease areas enhanced the known chemistry. Although being attractive as well as exciting at that point in time, some of the early AI companies may have as well over-hyped the kind of potential which these platforms held so as to transform drug discovery, hence generating a lot of skepticism as far as the ability of companies are concerned to deliver on the promises that were made.
The novel wave of AI platforms happens to be better poised so as to find out solutions to the issues when it comes to small molecule development by way of opening completely fresh chemical spaces, raising the probability of their success and at the same time decreasing the cycle time as well as the costs. All this is now a possibility due to major tech upgrades that have enabled the churning out of massive amounts of data on which the models can go on to get trained. Also, advancements in AI as well as computational power have all led to much better models which are indeed capable of exploring molecular structures which haven’t been seen before or have been regarded as drug leads – and also forecast as to how they would work. AI hence enables the sector to imagine two to three times better success rate when it comes to small molecules than what was possible before.
The point here is that AI is just about making its inroads into the I&I disease space; however, small molecules happen to be fast becoming as developable as biologics were around 2-3 decades back. Though the Inflation Reduction Act happens to give small molecules a much shorter period when it comes to protection against price negotiation as compared to biologics, thereby creating a so-called pill penalty, one may as well think that the efficiency gains that happen to be afforded by small molecule development that’s AI-based are going to offset the disincentive, thereby preserving the massive value of small molecules to the patients and also the overall healthcare gamut.
AI is indeed changing the spectrum of small molecule drug development throughout the board, nowhere more than in the case of I&I diseases. The tech is, of course, going to drive the major therapeutic developments when it comes to chronic I&I diseases in the decade to come by way of enabling exploration of small molecule drugs that can as well go on to offer options that are attractive to biologics and, in a way, be accessible to more patients across the globe.
