By John Davis 03 Aug 2020
Pipeline Watch is a weekly snapshot of selected late-stage clinical trial events and approvals announced by pharmaceutical and biotech companies...
Advances in multiple scientific areas will mature into novel therapeutics, often tailored for the individual patient and increasingly curative, making biopharma an exciting place to be in 2020.
For Scrip’s annual preview of the year to come, our journalists contacted more than 80 industry executives and experts for their views on the outlook for 2020. In the first in a series looking at those expectations, we focus on science and technology, and on highlighted therapeutic areas.
Much in evidence was positivity around scientific and technological advances; the promise of big data and real-world evidence as the sector becomes more sophisticated in its use of machine learning and artificial intelligence; and the progress of personalized medicine.
"We have seen unprecedented advances in the understanding of the biological underpinnings of disease over the past decade, and in 2020, I think we are going to continue to see an increasing number of those discoveries translated into new therapies that make a meaningful difference for patients,” said Nancy Simonian, CEO of Syros Pharmaceuticals Inc., which is developing small molecules to control gene expression.
One such expanding area of science, epigenetics, was highlighted by James Brown, CEO of Durect Corp..
“Big data will continue to transform the biopharma industry in the upcoming year. The advancements of next-generation sequencing tools and computational biology are accelerating, enabling rapid discovery of disease mechanisms. In addition, big data will continue to drive the construction of robust predictive models of gene expression and expression regulation that will reveal complex mechanisms of diseases not only related to genomic sequence, but epigenetic events. The epigenome is the chemical modifications to DNA and related proteins that regulate the expression of genes within a person’s genome without modifying the underlying sequence,“ he explained. “Epigenetic drug discovery programs have attracted increased attention in recent years. Novel therapeutic candidates against epigenetic targets continue to be discovered and have the potential to effectively reverse transcriptional and epigenetic abnormalities present in many human disorders, including cancer, metabolic, inflammatory, neurological and cardiovascular diseases.”
For Jason Coloma, president of Maze Therapeutics, “machine learning will show true impact to drug discovery and drug development pipelines.” Meanwhile, he added, “what’s old is new: pharmas and biotechs will focus even further on genetically validated targets in the clinic.”
The progress in understanding disease has been accompanied by advances in drug technology, both in terms of what is targeted and how it is targeted.
“Technologies such as gene editing and mRNA will continue to emerge as will technologies focused on personalized cancer vaccines,” predicted Daniel Menichella, chairman and CEO of mRNA-focused firm CureVac AG.
“We’re entering an era where it’s becoming possible to 'drug the undruggable' – moving beyond the narrow range of targets accessible by conventional methods, and intervening in disease by reaching new drug targets with innovative drug discovery approaches,” said Michael Gilman, CEO of Arrakis Therapeutics Inc., a firm developing small molecules to target RNA.
Bill Hinshaw, CEO of Axcella Health Inc., elaborated. “Continued advances in science are now allowing us to design therapies that leverage new learnings about fundamental human biology. We are now much more focused on developing treatments that reprogram or harmonize the body rather than suppressing or altering its functions. As a result, there is an increasing transition from your standard small molecule regimens to new potential options like cell therapies, gene therapies and endogenous metabolic modulators, which is our focus at Axcella. In 2020, I expect that we will see an expansion of these cutting-edge approaches.”
In parallel with the increasing sophistication of medicine comes the evolution of diagnostics. “Without a doubt, we’ll see the emergence of two themes: The first is a movement away from single-analyte biomarkers to multidimensional/multi-omic diagnostic approaches. The second is a movement away from centralized testing to a more distributed model, either IVDs or labs setting up their own laboratory-developed tests (LDTs) based on reagent kits and software tools,” said Jarrett Glasscock, CEO of Cofactor Genomics.
Cell And Gene Therapies
Jeffrey Leiden, chairman, president and CEO of Vertex Pharmaceuticals Inc., summed up the thoughts of many when he identified the key thing to watch for in 2020 as “additional clinical advances in cell and genetic therapies.” Many industry participants expect these technologies to be improved, expanded and applied to a greater number of diseases, although Maze Therapeutics’ Coloma fears “Gene therapy will continue to disappoint on clinical readouts.”
Others focused on the positive. “While we’ve made significant strides over the last few years, 2020 will cement cell therapy as a new modality to develop curative treatments to fight cancer and other disease,” declared Lalo Flores, CEO of allogeneic stem cell therapy developer Century Therapeutics.
Part of this will be about improving the technology: As Timothy Lu, CEO of Sentio Biosciences said, "2020 will see continued progress in cell and gene therapies in initial indications, but will also demonstrate the need for next-generation technologies that can provide greater specificity and control to enable transformative benefits for broader therapeutic indications."
“2020 is poised to be an exciting year for regenerative medicine with advancements like the launch of a Phase II osteoarthritis clinical trial anticipated to be one of the largest mesenchymal stem cell (MSC) trials to ever be conducted,” pointed out Ross Macdonald, managing director and CEO, Cynata Therapeutics. “Additionally, big players are expected to continue expanding their footprints in regenerative medicine, such as Takeda Pharmaceutical Co. Ltd., Astellas Pharma Inc. and Fujifilm Pharma Co. Ltd., with the latter planning to launch operations at its new induced pluripotent stem cell (iPSC) production facility in 2020.”
Novo Nordisk AS’s CEO Lars Fruergaard Jørgensen was also enthusiastic about stem cells. “We hope we can go into Parkinson’s disease with stem cell therapy and produce dopamine in these patients; that will probably go into the clinic sooner than our planned diabetes trial using stem cell therapy because diabetes is a more complex disease,” he said. The company is still at the preclinical stage but is aiming for a curative treatment.
For Martin Lehr, CEO of Context Therapeutics, “2020 will be the year of CAR-T in solid tumors. Will we finally see a breakthrough?”
A combination of cutting-edge genomics and state of the art cell therapy is the ideal approach to treating cancer, according to Iraj Ali, CEO of Achilles Therapeutics Ltd., which is focused on clonal neoantigens – mutated proteins that form early in tumor evolution – as a new drug target class to be targeted with immunotherapies.
Given the challenge that advanced therapies present in terms of scaling up and getting manufacturing right, he pointed out that newer companies like Achilles have been “created with manufacturing capability at the heart of the organization”, and are now benefiting from “the progressive thinking” that regulatory authorities adopted for CAR T-cell therapies approved in 2017 and 2018 for certain blood cancers. Achilles is now aiming to offer personalized cell therapy on a much larger scale. “We aren't interested in treating 10 patients, we're interested in treating 10,000 patients,” explained Ali. The advances of the CAR-T front-runners helped “shape the dialogue around the regulatory pathway for personalized neoantigen cell therapies in 2019, ready for a busy 2020 and beyond,” he said.
The treatment of cancer, which accounts for more than a third of activity across the pharma pipeline, was predictably a recurring theme for our industry participants. Several expect the year to herald advances beyond the current crop of checkpoint inhibitors.
"The therapeutic class of T-cell checkpoint inhibitors has transformed the treatment of cancer; however, a number of cancers do not respond to these therapies, including many blood cancers. Now, a race is under way to develop a new class of immune checkpoint inhibitors that unleash the innate immune system using macrophages. In 2020, we will continue to see the refinement of this technology in oncology, as well as, its application to conditioning regimens prior to bone marrow transplantation for gene therapies," said Mark McCamish, CEO of Forty Seven Inc.
Michel Pairet, member of Boehringer Ingelheim International GmbH’s board of managing directors with responsibility for the company’s innovation unit, emphasized that his company and the pharma industry in general have a vision of curing cancer. “Building on the momentum created by the first wave of immune therapies, we are getting closer to this ambition. This will be achieved by combining cancer cell-targeted approaches with the next generation of immune therapies. The field of cancer cell-targeted therapies, e.g. cracking KRAS cancers, continues with the possibility of the first clinical responses beyond G12C. In the field of immune therapies, we will be able to address tumors that are currently unresponsive to immune checkpoint inhibitors.”
“In cancer, as demonstrated by FDA’s approval of Roche’s Tecentriq in combination with Abraxane/carboplatin in non-small cell lung cancer, there will be more studies combining different combinations of conventional cytotoxic therapies with immunotherapies,” predicted Lew Bender, President and CEO, Intensity Therapeutics Inc. “As a result, new delivery technologies to improve drug safety and tumor killing will be of greater interest to both FDA and pharma.”
Ulf Jungnelius, Chief Executive Officer of Isofol Medical, thinks firms will seek out new opportunities to capitalize on the oncology opportunity. “Oncology is currently one of the most crowded spaces in biopharma with many companies working on late-stage immunotherapy solutions,” he said. “One major trend that I could see in 2020 is companies stepping back from the focused attention on competitive areas such as PD-1/PD-L1 combinations, where there are more than 2,000 currently active clinical trials, to focus on novel targets, new reformulations and therapies with broad applications such as early-stage cancer interventions. The earlier in a cancer's progression, and more importantly in a patient's treatment regimen, that we can effectively intervene the greater the potential impact.”
Daniel Passeri, CEO of Cue Biopharma Inc., which is developing therapies that selectively target and alter T-cells, said: “We are beginning to see the emergence of approaches for more selective, effective and better tolerated modulation of the immune system. In 2020, we should see continued progress toward this important objective.”
Nader Pourhassan, CEO of CytoDyn Inc., is another executive who identified immunotherapy as a key focus for the coming year. “We should expect more advancements in the treatment of metastatic cancers and immunotherapies in 2020,” he said. “Metastatic cancer is notoriously difficult to treat; however, breakthroughs in our understanding of how cancer uses the immune system has led to new avenues of treatment. Many of these therapies could potentially be used in combination to ensure the highest likelihood of success.”
The year will bring "continued efforts to demonstrate efficacy of immunotherapy (beyond checkpoint inhibitors) in solid tumors: CAR-T, bispecific antibodies, and neoantigen immunotherapy,” according to Andrew Allen, co-founder, president and CEO, Gritstone Oncology.
Doug Manion, CEO of Kleo Pharmaceuticals Inc., also sees broader progress coming in immuno-oncology. “A new wave of drugs that recruit the innate immune system to fight cancer with long-term success, but with potentially fewer side effects than T cell-based therapies such as BiTES and CAR-Ts, are something to keep a close eye on in 2020,” he said.
“These game-changing immuno-oncology drugs include next-generation, off-the-shelf Natural Killer (NK) cell therapies, Fc-enhanced monoclonal antibodies (mAbs) and drugs based on fully synthetic, bispecific Antibody Recruiting Molecules (ARMs) that recruit Immunoglobulin G (IgG) to bring NK cells and macrophages to cancer cells for rapid immune-mediated clearance.”
For Michael Kauffman, Karyopharm Therapeutics Inc.'s CEO, oncology R&D will continue to make headway in the more challenging cancers. “I expect 2020 to be another strong year for the biopharma industry and for oncology in particular, where drugs with novel mechanisms of action will hopefully continue to produce impressive clinical results and advance treatment options for some of the hardest-to-treat patient populations, such as those with relapsed or refractory multiple myeloma and advanced liposarcoma. Many companies, including Karyopharm, are expecting pivotal data in 2020 which could have a tremendous impact on the lives of patients with such serious and fatal diseases.
“Additionally, if we continue to see significant advances in patient care, I would expect investment in novel, yet validated, approaches to accelerate in 2020. Karyopharm’s novel XPO1 inhibitor, for instance, has been validated in multiple myeloma but we think this mechanism could be applicable to a host of other cancers. BCMA-targeting therapies are also of great interest in multiple myeloma and we expect to see more data from these programs in 2020,” Kauffman said.
There was also a focus on improving the treatment of cancer to spare patients toxic side-effects. “The recent progress in immunotherapy and new targeted therapies has been remarkable, resulting in blood cancer patients living longer and with better quality of life," said Gwen Nichols, chief medical officer for The Leukemia & Lymphoma Society. “As we move into this new decade, I feel optimistic we will continue to see less dependence on cytotoxic chemotherapies and more combinations of immunotherapies, targeted and standard therapies that home in more precisely on the cancer while sparing healthy cells.”
Robert Iannone, executive vice president, R&D at Jazz Pharmaceuticals, had a similar view: “I see great potential from combination therapies, especially in difficult to treat diseases such as cancer. I also anticipate a continued focus on evolving delivery technologies to improve the therapeutic index for effective treatments, to ultimately reach even more patients and address current unmet needs.”
On the personalized medicine front, Matthew Gevaert, co-founder and CEO, KIYATEC, sees the opportunity for reality to come closer to the hype. “A few clinical studies published in 2019 should be seen as bellwethers for the kind of personalized medicine that has been promised but not heretofore delivered,” he said. “A legitimate knock on much of the current implementation of personalized medicine is that it’s not tied directly to improved outcomes and there’s a lot of hand waving to get there so it has driven up costs without proportionally improving outcomes. Credible studies in 2019 demonstrate that, using advanced ex vivo models, an individual’s cancer cells grown in labs and treated with drugs can predict patient specific response at clinically meaningful accuracies."
“Though this has been used for some time in preclinical drug development, 2020 has the potential to truly be a game-changer in clinical implementation of personalized medicine, using this measured drug-on-cell effect to drive better outcomes for cancer patients," Gevaert continued. "What does this mean? By knowing individual patient responses to specific drugs prior to treatment, we will be able to improve outcomes under standard of care, and in trials better select who enrolls, enriching success rates. I believe that what we learned in 2019 will truly make a difference in 2020.”
Precision medicine advances were also highlighted by David Halbert, chairman, founder and CEO of Caris Life Sciences. “Molecular profiling will continue to significantly improve the treatment of people with cancer. Advances like RNA sequencing – the importance of which was stressed in the most recent National Comprehensive Cancer Network (NCCN) guidelines – help match patients to the right therapies and can determine if a tumor will respond to treatment before it’s prescribed. This knowledge will enable physicians and patients to make more personalized and precise treatment decisions, realizing the fullest potential of targeted cancer therapies."
Rabia Khan, Sensyne Health PLC’s chief of translational medicine, noted that 2019 saw Bayer AG launch TRK inhibitor Vitrakvi (larotrectinib) as the first “tumor-agnostic drug.” She said: “We are moving away from a world that defines a disease by its symptoms and towards defining disease according to the molecular pathology that has been perturbed.” Khan believes this will be game-changing. “The day will come where instead of calling it breast cancer, we’re calling it a TRK fusion-derived cancer, or instead of inflammatory bowel disease, it’s autophagy-driven autoimmune disease. Finding the molecular pathology that has been perturbed and using that information to define the Phase II and Phase III criteria will improve the success rate of clinical trials – reducing costs and getting drugs to patients faster.”
Others are hoping that progress in cancer will take the form of new therapies that treat it sooner or even prevent its occurrence.
“The field of cancer immunology will expand from creating therapies that treat cancer patients after they have been diagnosed to developing vaccines that inoculate healthy people against the disease and prevent it from ever occurring in the first place. A number of prophylactic cancer vaccines will begin clinical trials in 2020, and deliver data readouts. Positive results from these trials will drive a frenzy of investment into prophylactic vaccine development,” said Amit Kumar, CEO of Anixa Biosciences Inc., which is developing blood tests as well as CAR-T and vaccine technology for cancer.
While immunotherapy remains a key focus in oncology, expectations are high for its application in other diseases too. For example, “in addition to oncology, the development of immune therapies is starting to open new avenues to treat infectious diseases by stimulating the patient´s own immune responses,” commented Boehringer Ingelheim’s Pairet.
“The immune system normally exists in a balanced state, constantly recalibrating itself moment to moment. In the case of autoimmune disease, this balance is askew, the normal checks and balances insufficient,” said Rahul Kakkar, CEO of Pandion Therapeutics Inc. “In 2020, we expect to see the first approaches to tackling autoimmune diseases which move beyond cytokine and kinase inhibitors towards true immune rebalancing, and the use of strategies which move beyond the systemic towards localized immunomodulation."
“We see 2020 delivering significant advances in the treatment of immune-related disorders,” also commented Gregory Demopulos, chairman and CEO of Omeros Corp. “One such focus is complement-mediated diseases. To date, there are only two complement inhibitors on the market, both targeting the same protein. The complement system is increasingly implicated across an expanding range of disease areas, and biotech companies are now actively targeting an array of complement proteins. We expect next year will bring an FDA approval for the first drug to treat thrombotic microangiopathy, an often-fatal complication of stem cell transplantation, by inhibiting a novel complement target. Other unique complement-related development programs will also be entering clinical trials. These programs represent what biotech companies do well – develop small molecules and biologics for orphan indications, many life-threatening, that big pharma often won’t pursue, providing treatments for patients who otherwise would have none.”
Roger Tung, co-founder, president and CEO of Concert Pharmaceuticals Inc., is also looking past oncology in 2020. “I believe that biopharma innovation will continue to reach beyond its focus on rare diseases and cancer, to increasingly progress approaches for treating mainstream diseases that impact millions of people, such as mental illness, Alzheimer’s and autoimmune diseases.”
For Steve Paul, chairman and CEO of Karuna Therapeutics Inc., CNS will see a renaissance in 2020, driven by new biological insights. “We are on the brink of a golden era of new CNS medicines that will be catalyzed by small, emerging biotechs,” he said. “In 2020, we will see small companies leading innovation in neuroscience drug discovery and development and capitalizing on the fact that we know more than ever before about the biology of the brain and the intricacies of synaptic transmission and how this can be modified to treat both psychiatric and neurological disorders, such as depression, schizophrenia, Parkinson’s disease and Alzheimer’s disease. Recent positive trial results will spur increased investment and lead to a boom of new therapies in a very large therapeutic area that has been quiet, from an innovation perspective, for some 30 years.”
Travis Mickle, chairman, president and CEO, KemPharm Inc., expects there to be an uplift in R&D for attention-deficit hyperactivity disorder. “2019 was the first full year following Takeda’s blockbuster acquisition of Shire PLC. There were many angles to this acquisition, including its impact on the ADHD treatment space given the mixed signals from Takeda about its prioritization of Vyvanse and Adderall. As a result, innovation in ADHD treatment took a back seat despite patients and prescribers continuing to demand products that better address key needs,” he said. “I think 2020 could see ADHD regain the spotlight as new companies and new technologies emerge that have the potential to reshape the market.”
Glyn Edwards, CEO of Summit Therapeutics PLC, is enthusiastic about progress in treatments for bacterial diseases and sees 2019-20 as “the bottom of the despond” for the antimicrobial field. “There has been a change in the level of innovation – we’re seeing novel antibiotics, phage display, very exciting early-stage products. Companies like ours have new, much more narrow spectrum products to get around resistance, they’re more effective but are very kind to patients – they leave the microbiome in tact. It’s a general trend that we’ll see more of.”
But he urges companies to be more ambitious. “Industry needs to change, and do superiority trials. It has got complacent, running non-inferiority studies – if their product is better, they should do trials to show it. Physicians need to be shown,” he said. “There is also a need to develop products for indications where current treatments don’t work well,” rather than just developing products that are different but not better as a response to increasing antimicrobial resistance. “We’ve got quite a lot of alternative treatments coming through – now we need to incentivize big steps forward,” he said.
Meanwhile, “2020 will be an important year for NASH,” said Genfit SA’s CEO Pascal Prigent and president/COO Dean Hum, predicting the “first-ever drug approval with Intercept Pharmaceuticals Inc.’s OCA (obeticholic acid)” and the “availability of Genfit's NIS4 non-invasive diagnostic” as well as “long awaited data from [the] pivotal Phase III [trial] evaluating [Genfit’s] elafibranor in NASH.” They added: “Interestingly, it's quite clear that NASH will ultimately be a primary care market, given the high prevalence of the disease and the need to treat these patients with increased cardiovascular risk before they develop cirrhosis.”
Robert Wessman, founder, chairman and CEO of Alvogen Inc., also sees novelty in the primary care market. “We will continue to see more biologics coming for non-traditional biologic disease areas such as Alzheimer’s, asthma, allergy, HIV, Parkinson’s, etc. This will create stronger treatment options in the primary care segment."
John Butler, CEO, Akebia Therapeutics Inc., is excited about the “increased interest and investment in advances for patients with cardiorenal diseases. For instance, in 2020 we expect to see the science of the HIF (Hypoxia Inducible Factor) pathway, a discovery of how the body responds to changes in oxygen levels, advance toward enabling potential future treatment options for various conditions, including anemia due to chronic kidney disease. Three scientists shared the 2019 Nobel Prize for discovering the HIF pathway, which is a reminder that there is groundbreaking science behind all of our work.”
The emerging medical cannabis market will drive a growing segment of the pharmaceutical market, pointed out William Levine, founder and chief scientific officer of CannRx, who is also the founder of Izun Pharmaceuticals Corporation, a biopharmaceutical company specializing in botanical medicine. He predicted trends towards “increased data-supported targeted formulations with well-designed clinical trials. We need to know that the product can generate the expected effect,” as well as “controlled dosing based on better delivery systems – higher bioavailability with better control can enable lower doses with less side effects but same benefits.” He also expects the development of “better quality control systems to ensure product quality and safety.”
Forthcoming installments of this series will focus on business; policy and regulation; and the patient.
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