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The importance of life sciences companies focused on rare diseases to take early steps to bridge connections with patients, caregivers, and healthcare providers.

A Rare-Disease Must? Building Long-Term Relationships

Therapeutic companies that work with rare diseases must take early steps to build relationships with patients, caregivers, and HCPs.

Rare Diseases: Building Long Term Relationships 

With the role of Medical Information in pharma companies changing in recent years, this article outlines some current and future trends including globalization and the use of data to drive change.

Outlining Current and Future Trends in Medical Information

AbbVie Pedro Valencia ADCs

PE: How is AbbVie using novel cancer biomarkers to develop potential first-in-class ADCs for the treatment of advanced solid tumors?

We're constantly looking for biomarkers that can help us to do two key things. The first is to tackle cancer cells. and spare normal cells. We’re looking for specific antigens that are over-expressing tumor cells, and you see limited expression in normal cells. We want to make sure that target that’s over-expressed is critical for the survival of the cancer cell. Once you block it, you can actually drive a cancer cell death. That’s what we're looking for. In that perspective, c-Met is one of those biomarkers that is over expressing multiple tumor types such as lung, colorectal, gastric, and other GA tumors. We as an industry have tried to tackle c-Met in the past but have been unsuccessful. It would actually be successful to tackle what we call met, which is a gene inside the cell.

There’s this thing called met amplification, where the cancer cell produces multiple copies of the gene, and around 30% of patients have it. We can actually tackle that with small molecules. But once the gene becomes a protein and gets over-expressed in the cell, that over-expression is something we haven’t been able to target. For example, we know that on lung cancer, c-Met over-expression is about 25% to 50% in colorectal cancer, and it could be anywhere from 30% to 70% depending how you measure it, so it’s quite prevalent.

With ADCs, we’re trying to tackle c-Met over-expression on the surface of cancer cells. That was novel, and we can do it through ADCs. 706 has a target called SEZ6, and it’s a target that is over expressed in neuroendocrine cells or neuroendocrine neoplasms. When you think about it, multiple tumor types kind of have a subset of cells that are neuroendocrine driven. Small cell lung cancer is one of the few that has everything driven by neuroendocrine cells. The beauty of SEZ6 is over-expressing those cells and limited expression in normal cells. So, we can tackle it with an ADC and drive the results that we're seeing today.

PE: ADCs have redefined the treatment of cancer in recent years. Can you please discuss the promise of this emerging class and what the future may hold?

At the end of the day, ADCs work like a trojan horse. You have a good antibody that cancer cells are happy to receive, but once you hook into the cancer cell receptor, you deliver the payload, which is pretty much chemotherapy. It’s actually a highly potent version of the regular chemotherapy cancer patients are given on a regular basis. So, from that perspective, our goal is to replace chemotherapy. Our grand goal with ADCs is to replace good old, decades old chemotherapy that is really toxic for some patients. That’s how we see the redefinition of cancer treatment in the future with ADCs. So, what do we see in the future? Well, if you think about it, chemotherapy is being given in combination with other agents. In the future, we see ADCs being given in combination with chemotherapy. There will be one with other agents such as immuno-oncology agents. So, if you combine the ADC and the PD1s, you can start seeing that synergy come together and kind of start really dreaming about cures for the patients. All in all, we're super excited about ADCs replacing chemotherapy. 

In an interview with Pharm Exec Associate Editor Don Tracy, Pedro Valencia, VP, Solid Tumor Pipeline Strategy & Execution, AbbVie, discusses using novel cancer biomarkers to develop potential first-in-class antibody drug conjugates (ADCs) and the promise that they offer. 

Utilizing Biomarkers to Develop First-in-Class Antibody Drug Conjugates to Treat Advanced Solid Tumors

Vivacelle Bio has launched a Phase III clinical trial for its leading therapeutic candidate, VBI-S, designed to treat hypovolemic septic shock. According to the company, the trial will be conducted across seven major septic shock treatment centers in the United States, which include some of the biggest septic shock treatment centers in the country. Investigators seek to compare VBI-S and standard of care (SOC) to SOC alone in a 1:1 ratio.

"Initiation of our Phase III trial is a significant achievement for our team following years of dedicated work developing our phospholipid nanoparticle technology platform," said Harven DeShield, PhD, JD, MSc, CEO, Vivacelle, in a press release. "Based on our excellent Phase II results, and the positive interaction with the FDA affirming our Phase III design, we are excited to initiate this pivotal trial of VBI-S to investigate its ability to improve blood pressure and reverse organ failure in hypovolemic septic shock, an area of immense need, which remains underserved by the current standard of care. We are grateful for the ongoing support from the U.S. Department of Defense and the NIH, and we look forward to working with the dedicated medical professionals and researchers across the various sites to advance this important clinical trial."

This open label, randomized, controlled trial, which has been cleared by the FDA, will include 40 patients who have not responded adequately to standard treatments and are on vasopressors. Those patients will have a SOFA score >/= 5 and also meet additional inclusion for a 48-hour treatment period. The primary endpoint of the trial is an increase in the mean arterial blood pressure (MAP) by at least 10 mmHg with a target of 60-65 mmHg. Vivacelle stated that patients in this trial will have failed attempts to raise blood pressure to a survivable level using standard fluids and will be on vasopressors, potentially resulting in life-threatening complications.

Previously, Vivacelle’s Phase IIa trial demonstrated 100% efficacy in achieving the primary endpoint of raising MAP by at least 10 mmHg and improving patient survival from 10% to 70% without severe drug-related adverse effects. Full results were published in 

VBI-S is based on Vivacelle's phospholipid nanoparticle technology, which works to redistribute nitric oxide to increase blood pressure in septic shock patients. The company believes that it has the potential to be the first successful treatment of septic shock that is mediated primarily by overproduction of nitric oxide. Previous research has suggested that endogenously produced nitric oxide plays a key role in the pathogenesis of septic shock.

"Treating patients undergoing septic shock remains one of the greatest challenges in the U.S. healthcare system and poses an even greater problem in other parts of the world amongst adult and pediatric patients. Given this need, we welcome the opportunity to continue our work with the Vivacelle team in their efforts to bring innovation to the front lines of critical care patient treatment," said Michael Moncure, MD, FACS, professor department(s) of Surgery of University Health/Truman Center, UMKC School of Medicine, in the press release.

The study is funded by the Naval Medical Research Command (NMRC) – Naval Advanced Medical Development (NAMD) program via the Medical Technology Enterprise Consortium (MTEC).

1. Vivacelle Bio Initiates Phase 3 Trial for Lead Asset VBI-S to Treat Patients with Hypovolemia Due to Septic Shock. 

July 23, 2024. Accessed July 23, 2024. https://www.prnewswire.com/news-releases/vivacelle-bio-initiates-phase-3-trial-for-lead-asset-vbi-s-to-treat-patients-with-hypovolemia-due-to-septic-shock-302203465.htmln 

The trial is expected to include 40 patients across the United States who haven’t responded adequately to standard hypovolemic septic shock treatments and are on vasopressors.

Vivacelle Bio Launches Phase III Clinical Trial for VBI-S to Treat Hypovolemic Septic Shock

Video interview with Peter Wahl from CorEvitas

Making the Grade: Registries as Sources of Regulatory-Grade RWE

Registries are used for multiple purposes, from peri- and post-approval safety studies to comparative effectiveness studies. With choices that include multi-sponsor registries, bespoke registries, nested studies, and more, how should you determine what works best for your needs? What do regulators say about using registries to inform decision making? Industry expert Dr Peter Wahl, MLA, MS, Global Head of Scientific Affairs at CorEvitas, part of the PPD clinical research business of Thermo Fisher Scientific, explains registries and how to choose the type that best meets your needs and requirements. Watch to learn more about: 

What types of needs are met and what questions are answered by using a registry, and which registries are available;

What to look for in a registry and how to choose the registry type;

What the company sees in terms of regulatory requirements as they relate to registries, and examples of use cases for CorEvitas Registry data.

Dr Peter Wahl, MLA, MS, Global Head of Scientific Affairs at CorEvitas, part of the PPD clinical research business of Thermo Fisher Scientific, covers key considerations for choosing registries.

Fabrice Chouraqui, CEO of Cellarity, discusses some other potential areas where Cellarity's approach could be particularly impactful.

Potential Use for Sickle Cell & Liver Disease

What are some other potential areas where Cellarity's approach could be particularly impactful in developing new treatments in areas like sickle cell disease and liver disease?

Since we are focusing on cellular dysfunction, and that the vast majority of disease stem from a disorder at cell level. The Cellarity platform can be applied to virtually any disease now, in a world where you can do anything, you cannot do everything, you have to be extremely diligent in the way you allocate your capital when you are actually a startup or a young biotech like Cellarity. That's why that after an initial period where we had we have road tested our platform in different therapy areas ranging from respiratory to immuno-oncology, from metabolic disease to Heme, we've decided to focus our attention onto two areas, Heme, hematologic disease, and immune immunology. We decided to do so because these are areas where we can access bio sample easily. Since for us, everything starts actually by sequencing tissue, it's important to be able to access high quality bio samples, and it's much easier to access blood than long epithelium, for instance. So that explains our current focus. Also, these are disease in which you can find many conditions where there is a direct correlation between the disease, per se, and cell lineage differentiation. So, it's a great way to actually demonstrate the value of our platform quickly.

Now the platform can do much more, and we've been leveraging partnership with big pharma companies to expand the use of our platform. We are extremely happy to actually start this collaboration with Novo Nordisk, the world leader in metabolism, and that allowed us actually to apply the platform in a complex disease like metabolic dysfunction-associated steatohepatitis (MASH), and leveraging Novo Nordisk expertise built over decades, you know, in metabolism, as well as bio sample that they were able to gathered during technical trials in less than a year using the Cellarity platform and the science that we have developed, were able to identify novel insights in the biology of MASH, which created huge excitement at Novo Nordisk level. And so that's the way we are using to expand our the use of our platform beyond HEME and immune we are actually in advanced conversation with a couple of large pharmaceutical companies about doing similar partnership in these areas in which they have built tremendous expertise over decades, so we can retake the best of the two worlds, the expertise of the partnership bio sample they have gathered in clinical trial, as well as the uniqueness and the power of the Cellarity platform to uncover novel biology that you can drug and come up with drug candidates that are non-intuitive and would not have been able to be generated if we had used common drug discovery approaches.

In this part of his Pharmaceutical Executive video interview, Fabrice Chouraqui, CEO of Cellarity, discusses some other potential areas where Cellarity's approach could be particularly impactful.

The FDA has granted Orphan Drug Designation to Mabwell’s 7MW3711, a novel B7-H3-targeting antibody-drug conjugate (ADC) for the treatment of patients with small cell lung cancer. According to the company, 7MW3711, which features an antibody molecule, a novel linker, and the new payload Mtoxin (TOP1i), binds to tumor cell membrane antigens, being internalized and transported to the lysosome, releasing a cytotoxic drug, and inducing tumor cell apoptosis.

According to preclinical studies, 7MW3711 offers greater tumor-killing effects compared to similar ADCs and shows a favorable safety profile and pharmacokinetic properties, with controlled on- and off-target toxicities in animal models.

“IDDC is a next generation ADC site-specific conjugation technology platform independently developed by Mabwell, consisting of multiple systematic core patented technologies including the site-specific conjugation process DARfinity, the site-specific linker IDconnect, the novel payload Mtoxin, and the conditional release structure LysOnly,” reports Mabwell, in a press release. “The next generation ADCs developed based on the above systematic patented technologies have better structural uniformity, quality stability, efficacy, and tolerability. The novel payload Mtoxin (MF6) demonstrates good pharmacodynamics, bystander killing efficacy, and anti-multidrug resistance.”

Last year, the ADC market was estimated to be worth around $9.7 billion, with the expectation that it will reach $19.8 billion by 2028, growing at a compound annual growth rate of 15.2% from 2023 to 2028, according to MarketsandMarkets. This can be credited to a growing number of collaborations and partnerships among stakeholders in the market, a higher focus on the development of new ADCs, and regular approvals by the FDA, according to the report. Specifically, the Asia Pacific region is expected to experience rapid growth in the coming years, influenced by a growing number of ADCs among the patent population.

“The antibody drug conjugates market is competitive, with a small number of players competing for market shares. F. Hoffmann-La Roche Ltd (Switzerland), Daiichi Sankyo Company, Limited (Japan), Seagen Inc. (US), Gilead Sciences, Inc. (US), Takeda Pharmaceutical Company Limited (Japan), Pfizer Inc. (US), Astellas Pharma Inc (Japan), AstraZeneca (UK), ADC Therapeutics SA (Switzerland), ImmunoGen, Inc. (US), and Zydus Group (India), among others are some of the leading players in this market,” reports Marketsandmarkets, in a press release. “Most companies in the market focus on organic and inorganic growth strategies, such as product launches, expansions, acquisitions, partnerships, agreements, and collaborations, to increase their product offerings, cater to the unmet needs of customers, increase their profitability, and expand their presence in the global market.”

For years, tumors have been treated through chemotherapy and radiotherapy, which can cause damage to healthy tissue in the process. Puja Sapra, SVP, biologics engineering, oncology targeted delivery, AstraZeneca, stated that ADCs offer promise in treating cancer tumors, suggesting that they can act as a guided missile through delivering a powerful payload directly into cancer cells.

“These molecules consist of an antibody attached via a chemical linker to a chemotherapy payload,” said Sapra, in an article published by AstraZeneca. “When administered, the antibody part of the molecule homes in on tumor cells that express a specific tumor associated or overexpressed protein on their surface. The ADC is then taken into the cancer cell, where appropriate cleavage mechanisms release the cytotoxic payload. This process kills the cancer cell in a more targeted way than traditional chemotherapy, sparing healthy cells.”

1. FDA Grants Orphan Drug Designation to 7MW3711. 

July 16, 2024. Accessed July 18, 2024. https://www.prnewswire.com/news-releases/fda-grants-orphan-drug-designation-to-7mw3711-302198021.html

2. Antibody Drug Conjugates (ADC) Market worth $19.8 billion | MarketsandMarkets. 

October 5, 2023. Accessed July 18, 2024. https://www.prnewswire.com/news-releases/antibody-drug-conjugates-adc-market-worth-19-8-billion--marketsandmarkets-301948054.html

3. Engineering novel cancer treatments: ADCs and radioconjugates. 

October 18, 2023. Accessed July 18, 2024. https://www.astrazeneca.com/what-science-can-do/topics/next-generation-therapeutics/engineering-novel-cancer-treatments.html

Novel drug 7MW3711 binds to tumor cell membrane antigens, being internalized and transported to the lysosome, releasing a cytotoxic drug, and inducing tumor cell apoptosis.

FDA Grants Orphan Drug Designation to Mabwell’s Treatment of Small Cell Lung Cancer

As the CEO and founder of VeriSIM Life, Dr. Jo Varshney has plenty of experience using AI to solve problems. She recently spoke with Pharmaceutical Executive about how the technology is being used across the industry to discover new molecules and potential indications for existing treatments.

Pharmaceutical Executive: Some companies are using AI to discover new indications for existing drugs. How will this impact the ways that pharma companies utilize re-innovation?

 Using AI to repurpose existing drugs is a great application of the technology. We’ve seen a lot of interest in repurposing from pharma companies with drugs coming off of patent protection. AI can reveal hidden patterns in drug engagement ideally suited, perhaps with formulary modifications, to new indications. A great example of this is our PulmoSIM Therapeutics subsidiary’s drug asset PT-001. This molecule was repurposed from its previously approved use for the treatment of the rare disease pulmonary arterial hypertension. And with AI, we’ve been able to move it through preclinical development in half the time it would take traditionally.

PE: Is AI discovering new ways to organize massive data sets?

 What I would say is that AI is helping humans to 

massive data sets in new ways. AI algorithms are particularly well suited to find meaning in data sets that lack detail and consistency. This opens up new possibilities previously unexplored. For pharma companies, it empowers answers to questions like, “What’s the right formulation strategy?” or “What would be a good dosing regimen?” for a prospective drug candidate, long before initiating in vivo experimentation.

PE: Algorithms can retrieve specific points of data from massive sets with incredible speed. How is this impacting research/development timelines?

 This is a huge advantage to using AI in the preclinical drug development process. The conventional methodology features a lot of compartmentalization of teams and data, and sequential experimentation. It impedes efficient and informed R&D decision-making. AI systems like ours can analyze multiple dimensions of a drug candidate in the context of its intended target in parallel–not sequentially–in an integrated. Our BIOiSIM platform actually synthesizes several measures of a drug’s anticipated therapeutic effect into a single score we call Translational Index. This makes R&D much more efficient and candidate development less risky.

PE: How is AI able to take data sets in different, potentially incompatible formats, and present a unified story?

 The usefulness of an AI system is largely dependent on the data available to it. This is a major challenge and requires a strong data and validation environment to yield an accurate unified story. You’ve probably heard about “bias” in AI systems–like facial recognition systems that exhibit extremely error rates at identifying certain under-represented populations? If the validation environment doesn’t catch that an underlying training set is biased, your system’s analysis won’t be trustworthy. This is why regulators like the FDA have emphasized the importance of explainability in the use of AI systems for drug development. It’s important to ask AI technology partners to demonstrate they have these safeguards in place.

PE: How effective is AI at finding new molecules?

 Very. ChatGPT has shown us all that generative AI systems can be extremely realistic and intelligent when asked to create content like images and videos. AI-based LLMs are now also being applied to novel molecule generation. But while this approach can synthesize a large volume of new chemicals and protein structures faster, it often creates physically improbable drugs, or drugs that are so complex they might be considered unnatural or impossible to successfully reproduce. The big challenge for the use of AI in new drug design is biological validation. Without constraints based on clinical efficacy, selectivity, toxicity, etc. the risk to drugmakers is chasing even more dead-end candidates.

Dr. Varshney discusses how AI is being used to sort data and discover new molecules and indications for existing drugs.

Mary Anne Greenberg

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