Kamil Tamiola’s approach to better understand disease-causing proteins reflects his passion to study protein disorders.

Intrinsically disordered proteins (dubbed IDPs) and intrinsically disordered regions (IDRs) occur in one-third of the human proteome. Disordered proteins are shape-shifting and lack a consistent 3D structure. As a result, IDPs cannot be visualized using existing experimental methods, such as microscopy and mass spectrometry, or by predictive modeling approaches. Determined to “see” the invisible in the disordered proteome, Tamiola and his team have used interdisciplinary collaboration to address this longstanding challenge.

Tamiola had an opportunity early in his career to collaborate with researchers studying proteins implicated in progressive neurodegenerative disorders, like human alpha-synuclein and tau.

He explained, “It became evident that my expertise alone could only make a limited impact, and the true excitement lay in bringing together multiple disciplines.” The interdisciplinary collaboration was a significant shift for Tamiola, transitioning from solo physicist to cross-functional collaborator working closely with biologists and protein engineers. It was through this blending of different scientific disciplines that Peptone was born.

Peptone’s approach combines experimental and computational methods to study IDP molecular motions and their implications in biology. In a competitive landscape where some companies are using traditional approaches to tackle these challenging targets, Tamiola believes “Peptone’s technology can redefine what is considered “undruggable” into potential therapeutic opportunities.”

By leveraging proprietary tools to study protein shape and behavior before pursuing binding studies, Peptone can build more reliable models for drug discovery. This parallels the shift that X-ray crystallography brought to folded proteins, where understanding structure led to computer-aided molecule design.

What motivated you to start Peptone?

The idea stemmed from realizing the underexplored potential of IDPs while collaborating in academia.  Historically, drug discovery against disordered proteins involved screening, identifying binding molecules and then refining them through tools like NMR spectroscopy. With a bit of luck, we recognized how little effort had been devoted to this incredibly important class of proteins and set out to develop drug candidates that would bind to these proteins and exert a biological effect.

We began with some thrilling results that came out of proof-of-concept studies with pharmaceutical partners. We demonstrated the transformative power of using computers to alter the properties of disordered proteins and yield empirical results, all achieved without the existence of our own laboratory at the time.

These successful early endeavors motivated us to establish a dedicated laboratory, where we now engage in truly original research, and that was the moment that marked the inception of Peptone.

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“It became evident that my expertise alone could only make a limited impact, and the true excitement lay in bringing together multiple disciplines.”

Dr. Kamil Tamiola, Founder & CEO, Peptone

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Why is understanding the structure of intrinsically disordered proteins so important for advancing human health?

Intrinsically disordered proteins are widespread in the human proteome and across all life forms. They serve the purpose of enabling proteins to exhibit diverse, dynamic, and plastic structures to fulfill complex cellular functions. Unlike proteins with a singular function, these proteins collaborate with partners and can assume various structures. Considering the role of IDPs in numerous biological functions, both inside and outside the cell, there is a vast array of potential therapeutic targets.

IDPs are a large and diverse group and early research focused on neurodegeneration. This interest arose from the observation that bizarre, yet structured fibers found in human brains caused Alzheimer’s. Notably, the molecules forming these fibers lacked any inherent structure themselves.

Today, we recognize that in oncology, cardiology, autoimmune diseases, and even weight loss, disordered peptides play a crucial role – highlighting the broad relevance of disordered proteins across various therapeutic categories.

What makes you most hopeful about Peptone’s future?

We are seeing incredibly exciting data coming out of our programs and it is abundantly clear to us that this technology that we first developed for biologics research can also be successfully applied to small molecule drug discovery for intracellular targets.

As you read this, we are generating a wealth of data on challenging disordered targets showing great promise with clear therapeutic hypotheses. Our innovative insights position us to create best-in-class or first-in-class solutions. This is incredibly exciting as it allows us to revisit areas where people acknowledged the importance of a target but lacked a starting point. With Peptone’s unique approach and supporting data, we can now confidently guide progress.

How do think about the impact your early research can have on humankind overall?

I’m a humanist, and I believe in the value of humankind. And I still believe even with AI advances there will be a space and place and purpose for us in this world. Most importantly, I hope that companies like us, irrespective of how prolific we’ll be, will move the needle towards a better understanding of all these debilitating diseases and to giving people a better life.

What’s one lesson you’ve learned so far as CEO and founder?

Drug discovery is incredibly difficult with so many things that can go wrong. As much as we wish that we could reduce it to engineering and technological problems, I just don’t believe in that. What is incredibly humbling is the tremendous amount of artistry, devotion, and drive that individuals in the company must have, especially when there’s a challenge.

It is important to have a team that is motivated, almost obsessed with details, and in the face of setbacks, can find the inspiration to repeat experiments, look once again over data, and push in advance. So as CEO, my biggest responsibility is to communicate the progress of ups and downs transparently and concisely so we can make sensible decisions.

Who is someone who’s had the most professional impact on your career, and why?

I have two mentors. One is Dr. George Golumbeski and the other is Dr. Andrew Allen, both members of Peptone’s board of directors. Golumbeski is known in the drug discovery field as one of the most prolific deal makers who was key in the acquisition of Celgene by BMS. Andrew Allen is a professional chairman of our company but also an entrepreneur and clinician himself. They are both incredible people and play a vital role in shaping how I run the company and how I think about drug discovery. I call them my sounding board when it comes to decision-making, but also strategic thinking. Sometimes it is not even by giving me direct feedback, but by sending an article or a podcast saying, “Listen to this, look like these guys did it, what is there for us?” So, providing a learning experience in a variety of ways and I’m very, very grateful for that.

What’s one regular habit of yours that’s integral to your professional happiness and success?

Daily grand piano practice and reflection are very very useful. They really help me to calm down and focus and allow me to put myself in a sort of sensory deprivation mode to counteract all the stimuli I am exposed to daily. I’m also very committed to getting seven to eight hours of sleep every night and that is one thing I would recommend to anybody.

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“It was really striking to me how little research and development was going on despite how serious these diseases are. Many of them are deadly, and patients have very few treatment options. I thought that there was a lot of good that I could do personally to try to bring some new treatments to market.”

There are more than 200 types of Interstitial Lung Diseases (ILD), and the most severe cases, which include Idiopathic Pulmonary Fibrosis (IPF) and Progressive Pulmonary Fibrosis (PPF), have a patient survival time closer to 3-5 years from diagnosis without a lung transplant. The disease severity is what sets the life expectancy apart for IPF and PPF and currently approved therapeutics for these respiratory illnesses can slow disease progression but carry significant side effects that limit their use. Baranowski saw an opportunity to address a large unmet need and eventually made her way to Avalyn Pharma, which was built on the mission to develop inhalable medicines that minimize systemic exposure and are more precisely targeted to the lungs. She feels she can have the most impact serving in roles at smaller companies, where “you can really see and feel the outcome of your day and how you spend time in terms of driving the company forward.”

On the heels of Avalyn’s tremendous success with an oversubscribed $175 million Series C financing in September 2023, Baranowski shares more about her background, leading and advancing Avalyn, and insights into her leadership style.

What motivated you to join Avalyn Pharma?

My career began at Novartis, where I primarily focused on the commercial, financial, and strategic aspects of the business. It was there that I was exposed to the significant unmet needs in lung diseases, particularly in rare conditions like pulmonary fibrosis, cystic fibrosis, and pulmonary hypertension. I observed the lack of research and development in these areas and recognized the severity of these diseases, often with limited treatment options.

Driven by a desire to make a positive impact, I left Novartis to work at a New York family office involved in venture capital-style investing. My biggest investment in those years was in Pearl Therapeutics, a company working on combination therapies for asthma and COPD. This experience provided valuable insights into inhalation drug delivery.

Over the years, I discovered my passion for working in smaller companies, building teams, drug pipelines, and making a difference. Despite limited resources, I found it rewarding to be entrepreneurial and witness the tangible impact of our efforts. I was heavily involved in the respiratory therapeutic area which is why my passion for addressing rare lung diseases continues to grow and I’m excited about the potential to make a positive impact in this field.

What differentiates Avalyn from other IPF and ILD players in the industry?

Most lung-focused companies still prioritize systemic drug delivery and in the case of IPF, inhaled delivery is a distinctive approach. At Avalyn, we focus on pulmonary fibrosis, a deadly disease that falls under the umbrella of interstitial lung diseases, and despite its severity, there are only two approved drugs for this condition, pirfenidone and nintedanib, both of which are administered orally. These oral medications are often poorly tolerated, leading to a high rate of discontinuation, with only 30% of patients in the U.S. taking them.

Our therapeutic focus is to improve treatment by delivering these drugs through inhalation. This approach enhances drug concentration in the lungs, improving clinical efficacy, while reducing systemic exposure, resulting in better tolerability. Inhaled delivery is itself incredibly challenging and complicated, so you really have to think about the way to deliver the medicine, how often you deliver the medicine, what the formulation is, and what the device is. It has the potential to make effective drugs more accessible and tolerable for patients, potentially extending their lives and improving their overall health. This shift in perspective is a learning curve for our field, and we hope the market will follow suit, positioning us for future success.

Avalyn’s executive leadership team and board of directors is 50% women. What’s that like, and how does it compare to the industry as a whole?

Are there any companies in our industry whose board is half women? I don’t think so. I’m incredibly proud of that. We’ve also just hired a bunch of fabulous women who aren’t necessarily on our leadership team but are VP-level. I care about hiring people who care about their jobs and patients, and I think that’s again, the right way to align as a team and be motivated.

What advice would you give to the next generation of female leaders?

Do not shy away from being empathetic. As a woman, it is important to remain committed to embracing this part of our identity. I believe in being authentic and accept that it’s perfectly fine for me to get a little emotional when a patient shares their story with us. Making a difference for patients is what drives me and I’m often touched by the stories they share with us about what living with their disease is like.  It’s a natural and genuine response, and I’m proud of it.

What’s been the most rewarding part since joining Avalyn in 2022?

I love telling the story of the company, so it’s a lot of fun for me to sit down with doctors,  investors, analysts, or people we’ve recently hired at Avalyn and tell them what we’re up to. It’s empowering to watch people go from not fully understanding to a moment of excitement and realization of the impact we can have.

We also just completed a $175 million financing at the end of September which feels like a huge accomplishment, especially in today’s market, and has enabled me to start hiring great people.  Whether it is people that I’ve worked with before or have always wanted to work with, it feels great to now have an incredible team that we’re building and together, we’re going to do a lot of good for a lot of patients. At the end of the day, 95% of the fun I have at work has to do with the people I work with and how much I enjoy working with them.

What’s one lesson you’ve learned so far as CEO?

Don’t be afraid to be passionate and be yourself. I’m genuinely passionate about what I’m working on, and I know it translates to my peers because I’ve been told it’s infectious. If you can do that and lean into what you’re good at, then people respond to it. And, if you don’t know the answer, that’s okay. Ask your colleagues for help, advice, and feedback.

How has F-Prime been supportive during your tenure as CEO?

When I started at Avalyn a year ago, F-Prime’s Ketan Patel and Brian Yordy were invaluable and provided me with essential context regarding our historical data and the market’s overarching trends. They both possess a unique perspective when interpreting data, which enriched my own understanding and enhanced my capabilities.

How would you describe your leadership style?

I am very much a lead by example kind of person. I love talking things through and collaborating and getting people’s input. If I have a strong opinion, I’ll tell you, but often I like to hear from the team, and I think people like to be heard. At Avalyn, we’re all about integrity and keeping the patients that we’re trying to serve at the center of our focus. To me, that’s the right thing to do, but it is also the right thing for our business. If we can make decisions about how to develop our drugs with patients in mind, it means we bring drugs to market that are going to be able to impact their lives positively.

At the end of the day, we all work in this industry because we care about making a difference in patients’ lives and if we can keep that as our driver and our mission, it’s a great way to remind people of why we all wake up in the morning and what we’re trying to do together.

What makes you most hopeful about Avalyn’s future on the heels of a successful series C fundraise?

We’re in the process of launching a significant clinical trial for inhaled pirfenidone (AP01), and our focus is on diligently executing the study startup. This trial is set to be a large, well-controlled global effort, representing a crucial step forward for inhaled pirfenidone’s path to market, which is a very exciting development.

The capital we just raised also allows us to do the next stage of work with AP02 (inhaled nintedanib), which is the second lead clinical asset, and continue our efforts on the preclinical work for the fixed-dose combo of the two together. By transitioning from one mechanism to two, this combination therapy has the potential to revolutionize our field.

A lot of exciting initiatives are going on and it is my priority to build the company, grow the team, and do all the important work to set us up for success for the next stage.

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What does it mean to be CEO? It is more than holding the highest-ranking position in an organization. It is becoming a business builder.

In a way, all CEOs have the same responsibilities — expanding the company, collaborating with the board, engaging stakeholders, defining strategy, and creating a positive culture. However, the way in which one approaches these tasks is a means to stand out from the crowd.

Emanuele Ostuni is founding CEO of ARTBIO and worked closely with Roy Larsen and ARTBIO’s investors to build the company and its business model. Previously, he was head of Europe for Cell and Gene Therapies at Novartis Oncology, where he oversaw all commercialization aspects for Kymriah in Europe, the first FDA-approved CAR-T cell therapy.

For Ostuni, he never spent time in radiopharmaceuticals, but his role at Novartis had overlapping complexities. The products they were pursuing were multifaceted to make, deliver, and administer and he got satisfaction out of sorting through how to simplify it for patients, physicians, and ultimately payers. He felt his best when he was managing something multi-dimensional.

He explained, “The potential for efficacy in radiopharmaceuticals is high and there is an opportunity to build a platform, establish a supply chain and create a differentiated pipeline that allows ARTBIO to stand out from what the rest of the industry is doing.”

As ARTBIO launched in June 2023 with a $23 million seeding financing, Ostuni shares what drew him to ARTBIO, insights into his current role including leadership style, and advises fellow CEOs to connect with each other since they are “the few people who really understand what we go through.”

1. What motivated you to join ARTBIO?

As a scientist and seasoned executive, I was really intrigued by the potential of the technology and the science behind the company. The radiopharmaceuticals industry is not as well developed as the rest of oncology and immuno-oncology offering an opportunity to extract some good wins for patients while at the same time moving the field forward in a meaningful way.

In my early conversations with the F-Prime team, they were very open about sharing what they were thinking about and allowed me to share my views on how my experience in CAR T could lend itself to the innovation that was required to bring forward radiopharmaceuticals. It became a joint project very quickly where everybody brought something. F-Prime identified the technology from the scientific founders and allowed me to assess how it could be pushed forward.

2. What differentiates ARTBIO from other RLT players in the industry?

Our choice of medical isotope was driven by what is best for patients to beat their cancer.  With that decision, we built backward to the technology needed to produce the isotope and have supply chain security – we are unique in that we also own and control the manufacturing of isotopes instead of relying on a third party.  Our manufacturing approach is distributed to match the dynamics of the isotope, instead of trying to force fit it into a centralized approach that is exposed to several risks as most others are doing – issues with that approach have already surfaced with a negative impact on patients.  Lastly, we created our own discovery labs to build a pipeline of new experimental therapies leveraging our ideal isotope manufacturing.  We are creating this important infrastructure in part alone and in part in collaboration with a focus on simplifying and improving the delivery of therapies to patients and hospitals.

3. What’s been the most rewarding aspect of ARTBIO coming out of stealth?

We recently attended the Society of Nuclear Medicine and Molecular Imaging’s 2023 Annual Meeting, and it was amazing to see the team in action. I am most satisfied when I see them succeeding and it really showed when we were there all together. At ARTBIO, we believe in the importance of teamwork, exchange, and collaboration to bring our field forward.

We were also having conversations with peers and investors, both on the ground and in the background, that gave me clarity that we have accomplished a tremendous amount. Since the fundraise, it is clear to me how our differentiation from competitors is emerging. We are inspired by the many advances and innovative ideas that our industry is working on and there are many unmet needs left to be addressed.

4. How would you describe your leadership style?

I tend to be a giver, and I start with trust.  I am also an experimentalist by nature and focus less on if something is right or wrong, but rather on having a robust approach and hypothesis.  If things do not work as well as we expected, I ask why? What is the learning so that we quickly adjust and reach our goals?

I also surround myself with deep experts who also have personal characteristics that I think are critical for our team. We are building a new space, and the way things worked in the past is not going to work this time around. I am looking for people who have expertise in neighboring areas of the business, and also the ability to learn what is going to be different about our approach from what’s been done in the past. I aim for people who are driven and those who are doing it in a humble way. They put the team before themselves, thrive on data and value the importance of being transparent.

5. What’s one lesson you’ve learned so far as CEO of ARTBIO?

As a giver, it is hard to stop, but as CEO I have had to learn to modulate and know when it is the right time to stop serving. The CEO role can be a bit lonely, but I prioritize understanding what my stakeholders need rather than what I need from them.

6. ARTBIO just launched, but are there any noteworthy goals that you as CEO are currently focused on achieving?

My number one focus right now is rounding out the team. We can fundraise, but we need the people who manage those funds. I want to bring people with the right know-how, and also those who have chemistry with the team that we have in place now.  Only the team can move the company forward.

As we work to optimize isotope manufacturing, therapy manufacturing, preclinical research, and clinical development, I need to make sure that all aspects move forward without becoming each other’s obstacle.

7. What is the best piece of professional advice you’ve ever received?

I have been blessed with many managers, peers, and direct reports who taught me a lot through their actions and words.  The quote that I always go back to that summarizes a lot of my learnings and attitude is by Winston Churchill: “Success is not final, failure is not fatal: it is the courage to continue that counts.”

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