Guest Column | October 23, 2024

Panavance Details IND Prep Ahead Of FDA Submission For Ovarian Cancer Trial

A conversation with Panavance Therapeutics CEO Greg Bosch

video conference team meeting-GettyImages-2095813137

All pharmaceutical companies, large or small or somewhere in between, understand the importance of engaging with the FDA ahead of an investigational new drug (IND) submission. Knowing this, Panavance’s experience developing misetionamide (GP-2250) is a good example of early engagement with the FDA. Panavance is working toward a clinical trial for this tumor cell-selective small molecule drug in combination with bevacizumab (bev) and pegylated liposomal doxorubicin (PLD) for the treatment of platinum-resistant ovarian cancer (PROC). It has already seen preliminary success with misetionamide for the treatment of pancreatic cancer. The results of a recently published study1 in the journal, “Cancer Medicine,” demonstrated a profound antitumor effect when used as monotherapy as well as synergistically when used either in combination with PARP inhibitors or bevacizumab (bev) in preclinical models. Misetionamide also has anti-angiogenic activity that interacts synergistically with bev.  Both findings, among others, strongly suggest that misetionamide in combination with PARPi or bevacizumab should be studied further as a new antitumor drug combination in ovarian cancers.

Panavance completed a pre-IND meeting with the FDA in May to review its ovarian cancer clinical development plan for a Phase 1/2/3 trial. Nothing went sideways during their chat with the FDA, and the experience gave the single-asset pharma company the confidence it needed to forge ahead with its IND submission planned later this year.

In this interview, Panavance CEO Greg Bosch discusses the company’s pursuit of a second trial for misetionamide, walking us through IND preparations, CRO selection, and the delicate balance of developing a drug and securing funding for its success.

Clinical Leader: Take us back to the time before the pre-IND meeting in May. What was the prep work for a pre-IND meeting?

Greg Bosch: We were very diligent in making sure that the scientific rationale was there — based on the safety of the drug that we've already seen in animal models, the ongoing pancreatic cancer clinical trial, and the multiple preclinical models as now published in over 20 peer-reviewed papers covering several different types of cancers showing a reduction in tumor size.  

As always, the FDA required that companies submit in writing the questions we wanted to discuss during the pre-IND meeting along with the reasons and the rationale behind the questions. Before the pre-IND meeting, FDA responded to the questions one week in advance of the meeting to give us time to review the information and prepare for the meeting. The FDA then gave us the option of either an in-person or virtual pre-IND meeting. Panavance participants included seven professionals, including outside experts. The FDA typically includes five to ten professionals depending on the focus of the questions with expertise ranging from statistics, pharmacology, toxicology, regulatory and clinical.

During the pre-IND meeting, we dug a little deeper into those questions. You really shouldn't go, “Well, now that we have this meeting, what we really want to ask is…” Because they want to be prepared, and they are governed by regulation. Often they will tell you, “This will be subject to seeing further data and will be a review issue.” We got out of the meeting exactly what we had hoped: clarity about how to structure our initial new drug application and especially to prepare for the Phase 1 study.

Specifically, a key focus was on inclusion/exclusion criteria, especially what treatments eligible patients in the clinical trial may/must have had prior to receiving misetionamide. The patient then discusses with their doctor to see if they are eligible and if they want to enroll in the trial. We, of course, understand the FDA’s rationale to prioritize approved treatments over treatments still in development. So our informed patient consent document will of course recommend following a doctor's advice, including considering all approved therapies, et cetera.

Between then and now, how much more work did you have to do to prepare for submitting the IND?

The bulk of the work is to write the details of what's happening at the sites where the clinical trial will be conducted. This includes for example, the informed consent for the patient, pharmacy protocol, blood draw sample protocol, testing, and lab guidance documents which need to be prepared as well as finalizing the treatment protocol.  

With most diseases, in Phase 1 clinical trials, you're often treating healthy volunteers. Because we're targeting cancer, we’re treating actual cancer patients. So, in addition to safety, you're really looking for some hint of efficacy in Phase 1. In fact, you usually need to see indications of efficacy to gain financial support to fund Phase 2.

Did you tap internal resources for all of those things, or have you contracted outside partners to help?

As an emerging pharmaceutical company, it's impossible to afford all the resources required with full-time employees and benefits. From clinical operations to regulatory to pharmacology to chemistry, manufacturing, and control, we have contracted partners we work with. We have some of those resources internally, but when you need deeper expertise, we go to a contract research organization (CRO).

For example, when we went to the FDA for our pre-IND meeting, we engaged a person who is both the head of regulatory at a leading CRO and a former FDA expert. For the final review of the clinical protocol, we're going to seek review by the practicing clinicians and the top experts, who went to the pre-IND meeting with us.

Have you had any particular challenges or lessons learned with this or the pancreatic cancer trial?

We pursued pancreatic cancer as the initial indication because of exceptionally good preclinical work and we wanted to address one of the hardest-to-treat cancers which has an urgent need for more effective therapies. Despite advancements in oncology, the five-year survival rate is just 10%, leaving patients with limited options. Given the high mortality rate in pancreatic cancer, recruiting patients and having them progress through the trial has been particularly challenging. We picked one disease, pancreatic cancer, while many phase 1 cancer trials are done first with an all-comers study opening up the trial to different types of cancers providing a broader pool of patients and the ability to move through the trial quicker to ultimately deliver another treatment option to patients.

Now, we're selecting our CRO and the biggest priority for any small biotech is financing and access to funding.  We have been very open and really direct with our CRO prospects to let them know that our goal is to be ready to engage, but we cannot sign a contract until we have secured funding. Communicating this information is important because the CRO must start work on the project as part of the proposal process. The key takeaway is to always be transparent with not only your CRO but all your vendor partners about what you can do, what you can't, and when you can do it.

In the first part of the new year, we hope to get into the clinic with the ovarian cancer trial. We have made significant preparations to prepare an IND application, select a CRO, and manufacture the drug product for dosing during the clinical trial. Initiating the actual trial is a function of financing at this point.

When choosing a CRO, what was your selection process?

Based on previous CRO experiences, we selected seven prospects to evaluate, which is a fairly large number. We prioritized CROs with relevant disease and clinical trial experience not just in gynecology, but ideally in ovarian cancer. We also surveyed former oncology company executives who just finished working on a newly approved ovarian cancer drug asking them which CROs they had worked with then and who they are working with now - - which was key in selecting the right CRO partner.

As an emerging pharmaceutical company, one of the biggest challenges is whether to pick a large, global CRO that can take you everywhere or the CRO that's more right-sized for you — the one where you’ll be able to get the attention of the top talent within the organization without competing for attention among CRO’s large pharma clients.

What then is the next milestone?

The next milestone for the ovarian cancer trial is submitting and getting the IND open by the end of the year. We may have to provide some additional information to the FDA, but we anticipate it should be pretty straightforward. The second major milestone is securing financing to conduct the trial.

Does the sigh of relief come with the IND being open, with the finances secured, or with both?

Getting an IND open with the FDA is a significant achievement. It says you knew what you're doing as a team, because it's a complicated and detailed process. Many companies are not able to progress into the clinic due to many potential challenges, so opening an IND is an important milestone, and we will certainly celebrate that.

The second, of course, is the financing. When the funding is secured, we can start to treat patients, and that's ultimately why we do what we do. If I had to put them on a balance, I would say certainly financing is the higher one just because it's less within our control.

With large pharma, the primary concern is often securing an approved IND. With Panavance being an emerging pharma company, you have to worry about both the IND and the funding. How do you approach that?

I've spent time on the big company side. Everyone no matter the size or the experience will tell you they don’t have enough capital. You have to prioritize how you are using resources whether you are a large or emerging pharma company. If a large pharma company had our asset, presumably they would be developing it in three, four, or five different cancers simultaneously. Their portfolio decision for example would be: do we go into prostate and triple-negative breast, colorectal and pancreatic, or lung and ovarian? Once that team prioritizes indications, they're already on the way. Securing capital for them probably happened in the prior year's budget cycle. Once the budget's approved, they're moving. We're chasing both the IND approval and the funding at the same time. But that's the nature of startup biotechs, you've got to step-by-step finance it.

My job as CEO is quite diverse with competing priorities. I am running the company and developing the clinical plan while also fundraising making sure we have enough resources to continue driving development. We need to have a plan outlining different scenarios around how quickly a trial can be completed and how long it will take to enroll patients while also considering what can happen throughout the trial.

Data drives funding. Positive data allows us to raise capital more easily while somewhat positive data makes us reassess the forward-looking plan. Negative data can mean the end of some companies if they have no other products or indications in the pipeline.

References:

  1. Kim MS, Glassman D, Handley KF, Lankenau Ahumada A, Jennings NB, Bayraktar E, Foster K, Joseph R, Lee S, Coleman RL, Sood AK. Mechanism and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer. Cancer Med. 2024 Aug;13(15):e70031. doi: 10.1002/cam4.70031. PMID: 39114948; PMCID: PMC11306972

About The Expert:

Greg Bosch brings over 35 years of healthcare experience to Panavance, with global leadership of commercial, operations, and R&D teams. His general management experience spans the pharmaceutical, biologics, biosurgery, and medical device segments, including acquisitions of public and private companies, private financings, and taking a company public. Before joining Panavance, Greg was CEO of Geistlich Pharma North America where he led a cross-functional team to achieve the market leadership position in regenerative medicine in the US dental field. While at Geistlich, he also led the company’s oncology program and was responsible for the team developing Panavance’s proprietary small molecule drug compound, misetionamide (GP-2250). Earlier in his career, he was the President and CEO of PuriCore PLC and held roles of increasing responsibility at Baxter International. Greg currently serves on the boards of Kibow Biotech and Panavance Therapeutics Inc. Greg earned his B.A. in Public Policy from Duke University and MBA from DePaul University.