Introduction

Wouldn’t it be nice if there was a way to increase the doses of chemotherapy to the tumor whilst at the same time reducing the dose for the rest of the body? This would be an ideal way to reduce its horrible side effects?

Well, RenovoRx (RNXT) has actually developed such a technology that it plans to use for solid tumors that are difficult to treat because they have no veins feeding them.

Their patented innovative drug delivery system called RenovoCath uses pressure to deliver chemotherapy agents to reach difficult-to-reach tumors by pressuring them through the walls of a nearby vein.

Doing so enables concentrating chemotherapy in otherwise difficult-to-reach tumors, increasing both the efficacy and lessening the side effects of chemotherapeutic agents.

The company has two clinical trials ongoing, a phase 3 trial for pancreatic cancer and a phase 2 / 3 trial for duct bile cancer.

Company Overview:

Phase 3 Lead Drig Product Candidate: RenovoGem

• Intra-arterial gemcitabine (chemotherapy) delivered through FDA cleared RenovoCath delivery system

• Phase 1, 2 and observational registry trial data demonstrated efficacy signals

• Phase 3 interim analysis based on patient deaths – estimated Q4 ’22 / Q1 ‘23

Targeted Approach: designed to decrease side effects and increase penetration

• Reduced systemic drug exposure compared to systemic chemotherapy)

• Higher local drug concentration

Novel Therapy Platform: RenovoTAMP

• Trans-Arterial Micro-Perfusion compatible with multiple small molecule chemotherapy drugs

Broadly applicable to locally advanced solid tumors

• Initial indications: pancreatic cancer ($1B addressable market) and cholangiocarcinoma)

• Potential future indications include non-small cell lung cancer, uterine tumors, glioblastoma

RenovoTAMP Platform: layers of market exclusivity (regulatory and IP)

• Orphan Drug Designation provides 7 years of market exclusivity for RenovoGem upon NDA approval

• 7 US patents issued on RenovoTAMP, delivery system, and drug/device combination

RenovoTAMP

Most solid tumors are easily reachable for chemotherapeutic agents as they have plenty of feeding blood vessels going directly into them:

However, there are solid tumors (like pancreatic cancer, duct bile cancer, locally advanced lung cancer, locally advanced uterine tumors, and glioblastoma) that often lack such a direct connection to blood vessels.

This makes these tumors difficult to reach with chemotherapy agents, the alternative is (S-1 registration):

"Trans-arterial chemoembolization (TACE) is an established first-line therapy for certain solid tumors. A key component of this approach is to identify and isolate vessels feeding the tumor, known as tumor feeders. However, in patients with pancreatic cancer, no tumor feeder vessels are visible during angiography. In the absence of visible tumor feeders, we can introduce drugs directly across the arterial wall into the surrounding tissue via pressurized diffusion."

Enter RenovoTAMP, their patented drug delivery system, which isolates nearby vessels and uses pressure in these to force the drug into the tumor.

How does that work? Here are the mechanics, from the S-1 registration:

"Our RenovoTAMP platform therapy utilizes pressure-mediated delivery of gemcitabine across the arterial wall to bathe the pancreatic tumor tissue in 120mL of saline with 1,000mg/m2 of the drug over a 20-minute delivery time (approximately a total of 1,500-2,000mg of drug dependent upon patient Body Surface Area). RenovoCath is an adjustable double balloon catheter designed to isolate the proximal and distal vessel and adjust the distance between the balloons to exclude any branching blood vessel offshoots."

The platform has a number of advantages, from the S-1 registration:

• Application of Approved Small Molecule Chemotherapeutic Agents: We use approved small molecule chemotherapeutic agents such as gemcitabine.

• Targeted Approach: With our approach, we have demonstrated in our clinical studies up to 100 times higher local drug concentration compared to systemic chemotherapy. We believe our approach decreases systemic exposure and improves patient outcomes.

• Delivery Method Independent of Tumor Vascularity: We invented a novel combination platform and delivery system to deliver small molecule chemotherapeutic agents in solid tumors resistant to systemic chemotherapy due to a lack of tumor blood vessels or tumor feeders.

• Broad Application for Solid Tumor Indications: Our platform is not restricted to a single small molecule chemotherapeutic agent or solid tumor type. As such, our platform and delivery system may be applied for use in additional solid tumor indications, including in solid tumors without identifiable tumor feeders.

Pipeline

The company has five conditions in its pipeline, two of which are in the clinical phase:

1. Pancreatic Cancer: Phase 3 TIGer Study (Q4 ’22 / Q1 ’23 Interim, Analysis, ’23 Enrollment Completion, 2H ’25 Data Read Out)

2. Bile Duct Cancer (Cholangiocarcinoma): Phase 2 CouGAr Study

3. Lunch Cancer: Pilot Animal Study Completed

4. Uterine Tumors

5. Glioblastoma

First and Second Indications: Locally Advanced Pancreatic Cancer and Hilar Cholangiocarcinoma

First Indication: Pancreatic Cancer

(Orhpan Designation)

• One of the deadliest cancers, with poor outcomes

• Pancreatic cancer is expected to quickly become the second leading cause of cancer related deaths

  • 5-year overall survival rate of 5-10% (Stages I-IV)

• In 2021 it was estimated that

  • 60,000+ Americans were diagnosed with pancreatic cancer

  • More than 48,000 died of the disease

  • Approximately 30% of patients have locally advanced pancreatic cancer (LAPC) and are not candidates for Surgery

Current Standard of Care

• Gemcitabine with Abraxane was approved in 2013 based on an 8-week survival benefit

• LAPC has approximately 12-15 month median survival

Second Indication: Hilar Cholangiocarcinoma (HCCA), Bile Duct Cancer (Orphan Designation)

• Cholangiocarcinoma (CCA) is a disease with an exceptionally poor prognosis

• CCA is the second most common primary malignant tumor of the liver with over 7,000 new cases diagnosed annually in the US.

• Based on the tumor location, CCA is defined as either intra-hepatic (within the liver) or extra hepatic (hilar cholangiocarcinoma, or HCCA)

Current Standard of Care

• Due to toxicity of the standard of care, a practice standard of care has not been established for HCCA

• Gemcitabine wiith cisplatin used in ABC-2 clinical trial

LAPC; Pancreatic cancer with RenovoGem

The most advanced is the company’s treatment for LAPC or locally advanced pancreatic cancer, with RenovoGem, which is a combination of an existing chemotherapy agent gemcitabine delivered via RenovoCath, the company’s patented delivery system.

RenovoRX Employs De-Risked Small Molecule Chemotherapy Drugs

First Drug Candidate: Intra-Arterial Gemcitabine

• IV (systemic) gemcitabine marketed in the US since 1996

• Established as part of a current standard of case for pancreatic cancer and other solid tumors

• Potent anti-tumor agent: cell phase specificity primarily killing cells undergoing DNA synthesis (S-phase)

• Pre-clinical studies: inhibits 80-100% of tumor growth with subsequent increases in lifespan

• Limitations of IV/systemic delivery include poor tumor tissue penetration and high systemic toxicity

RenovoGem (Intra-arterial Gemcitabine + RenovoCath)

• Intra-arterial gemcitabine for treatment of solid tumors

• FDA Orphan Drug Designation (7 years marketing exclusivity post-approval) for pancreatic cancer and CCA)

• Phase 1 / 2 and observational registry trial data demonstrated an increase in overall survival time in patients with LAPC

  • Median survival of 27.9 months) including radiation pre-treatment) vs. 12-15 months historical control

• Phase 3 interim analysis expected in Q3 ‘23

Mid-previous decade, the company held two clinical trials for RenovoGem:

Results: Phase 1 and II Clinical Trials

• To date, 43 patients treated with Intra-Arterial Gemcitabine using RenovoCath between the 2 studies from May 2015 to Dec 2018

• Average age of patient enrolled was 69.9 years

• Median gemcitabine dose was 1000mg/m²

  • Full 1000mg/m² dose administered to 33 of the 43 patient cohort

• On average, each patient received four intra-arterial treatments, ranging from 1-14 treatments

  • 13 of 43 patients completed the planned 8 treatments of IA therapy

• Reasons for early discontinuation of IA therapy:

  • Tumor progression (n=12)

  • Patient/Physician preference (n=8)

  • Serious adverse events (n=6)

  • Others (n=4)

• RR1 a phase 1 / 2 safety trial with 20 patients establishing a maximum dose of 1000mg/m² of intra-arterial gemcitabine delivered via RenovoCath

• RR2 Observational study produced a 29% survival (versus 12% for chemo) after 2 years.

It has to be said that these were not double-blind studies; the comparison in RR2 is made with an average based on historical data.

TIGeR-PaC Randomized Clinical Trial - Phase 3 Multicenter Trial

Trans (Intra-arterial Gemcitabine vs. Continuation of IV Gemcitabine and Nab-Paclitaxel following Radiotherapy for Locally Advanced Pancreatic Cancer (TIGeR-PaC) Randomized Clinical trial)

• _{Prospective multicenter randomized clinical Trial evaluating systemic therapy versus intra-arterial gemcitabine for pancreatic cancer}

• _{Primary Objective: Overall Survival from time of randomization}

• _{Secondary Objectives: PFS, objective response rate, duration of response, HR-QOL, degree of peripheral neuropathy, incidence of neutropenia, tolerability, and safety}

• _{Inclusion Criteria:}

  • _{Histologically confirmed pancreatic adenocarcinoma with initial diagnosis within 6 weeks of consent}

  • _{Locally advanced, unresectable disease, as defined by NCCN Guidelines}

  • _{ECOG 0-1}

These were encouraging results so they are now continuing with a phase 3 trial called TIGeR-PaC. The phase 3 TIGeR-PaC trial has run into some delays though after the company modified its SAP (statistical analysis plan) which it submitted to the FDA in June 2022. The main changes (from the 10-Q):

• (i) analyze only patients receiving SBRT, consistent with the protocol change made in December 2021,

• (ii) include a second interim analysis,

• (iii) change the total number of SBRT patients randomized in the study to 114 (a reduction from the original 200 patients) with a total of 86 deaths from SBRT patients, including all deaths from SBRT patients enrolled in the study before the submission of the Modified SAP, and

• (iv) repower the study from 90% to 80%, which is commonly used in clinical trials.

Originally they were also including IMRT patients but these had a higher dropout rate during the induction phase. In my discussions with RenovoRX CEO Shaun Bagai, he shared that management believes this will shorten the timeframe and significantly reduce costs.

The FDA has not yet signed off on the revised SAP though, in fact, they have not yet submitted the revised SAP, which will occur in Q1/23.

The first interim results will occur when 30% (26 of 86) of the total number of deaths have occurred and the second interim analysis will be at 60% (52 of 86).

On November 14 they had 37 SBRT patients with 114 in total needed, at this rate they expect all patients to be enrolled and randomized in 2025 with the final results out in 2025. But before that happens we get the interim results.

eCCA or extrahepatic cholangiocarcinoma

The company’s second condition for treatment with RenovoGem is eCCA or extrahepatic (or outside the liver) cholangiocarcinoma, cancer that occurs in the bile ducts.

There is already a significant amount of pre-clinical data supporting its effectiveness against this condition.

The company is putting together a phase 2/3 trial treating eCCA with RenovoGem and has already submitted the protocol to the FDA. Without any objection from the FDA, patients can start enrolling in Q1/23.

Market Opportunity

There is a $1 billion locally advanced pancreatic cancer market opportunity. $500 million in the US, and $500 million internationally, with an average new oncology drug pricing of $150,000 per year. (Source: Fletcher Spaght, 2019). There will be a prospective/formal pricing analysis conducted with Phase 3 data prior to commercial launch of RenovoGem.

This is for pancreatic cancer alone

RenovoGem gained an ODD or orphan drug designation from the FDA in 2018 for pancreatic cancer and for HCCA (bile duct cancer) in April 2021.

ODD provides the company with seven years of exclusivity to market intra-arterial use of gemcitabine for LAPC and ACCA upon New Drug Application, or NDA, approval.

Finances

The company is not generating revenues and won’t be for quite some time so cash burn is a prime indicator to assess.

There is not a lot of room here as they had $8.1M at the end of Q3 after they pocketed a net $14.6M with their IPO in August 2021. Their GAAP OpEx was $2.1M in Q3 and they lost $7.1M in operational cash flow YTD.

Management expects expenses to increase substantially as a result of the clinical trials, hiring additional research, development, engineering people and SG&A expenses, and defending their IP.

There are also 1.2M outstanding performance options, and 2.8M warrants (although with an exercise price of $10.8, they are far out of the money), so that’s 13M shares at $2.7 for a market cap of $35.1M or an EV of $27M.

We’re pretty sure that if the company becomes successful with at least one FDA-approved application for RenovoGem, but keep in mind this is a platform technology with potentially multiple use cases (not to mention it’s not necessarily limited to gemcitabine, the chemical therapy agent they’re using so far).

But we’re not there yet and won’t be for some time, 2025 at the earliest. Before that, they will have to go back to the financial markets and/or find a partner to help them with the clinical trial cost.

Conclusion

RenovoRx takes existing chemotherapies and makes them more effective and less invasive at the same time, by being able to concentrate most of the chemotherapy agent on the tumor itself, rather than letting it loose in the whole body.

All this with the help of its patented RenovoTAMP platform.

This is especially useful for tumors that don’t have feeders, and veins that go directly into the tumor, which is often the case with pancreatic cancer and bile duct cancer, the first two conditions the company is targeting with clinical trials.

Early results are promising, and the company received orphan drug designations for both conditions. But as always this isn’t guaranteed until phase 3 trials are concluded successfully and RenovoGem gets final regulatory approval.

This isn’t imminent, it will be 2025 at the earliest and until then the company will need additional financing and/or a partner with deeper pockets. However, there are two things that make the situation interesting for investors:

• The company’s core technology can be used in multiple conditions, greatly enhancing its potential commercial value.
• The market cap is a fraction of what the company could be worth when they get final FDA approval.

Originally published on TalkMarkets.

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Disclosure: The author has no position in any stocks mentioned.

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