The San Diego, California-based clinical-stage drug development company’s candidates are VAL-083, a small molecule chemotherapeutic agent for the treatment of glioblastoma multiforme (GBM), a lethal brain cancer and other solid tumors; and REM-001, a phototherapy for the treatment of cutaneous metastatic breast cancer (CMBC), among other indications.
“Median overall survival for newly diagnosed GBM patients is only 12 to 18 months. Less than 25% of these patients survive more than one year,” Kintara Therapeutics (NASDAQ:KTRA) CEO Saiid Zarrabian told Proactive in an interview. “Sadly, when the patients get diagnosed with the current treatments, it leaves a lot to be desired.”
Kintara’s VAL-083 impacts DNA in a different way than the existing standard of care, temozolomide (TMZ), which was approved in 1999 and has been generic since 2010.
“It’s been over 21 years since patients have had a new treatment option for newly diagnosed GBM,” said Zarrabian, who believes VAL-083 offers new hope for patients where other treatments may not be effective.
VAL-083 is a small molecule DNA-targeting agent that exhibits a novel mechanism of action that results in DNA double-strand breaks and cancer cell death.
“Given its unique mechanism of action, VAL-083 may be positioned to offer greater benefits to patients in the MGMT-unmethylated subset, which has historically responded poorly to standard of care,” analysts at Aegis Capital said in a recent note.
“Within the unmethylated setting, VAL-083’s mechanism of action circumvents MGMT-mediated chemoresistance and maintains cytotoxicity, which differs from TMZ, and may point to relative benefit in this difficult-to-treat patient population,” they added.
For VAL-083, the ability to cross the blood-brain barrier and overcome DNA-repair enzyme resistance combined with the agent’s affinity to be absorbed by cancer cells provides a mechanism of action that may provide better safety and effectiveness.
Significantly, VAL-083 represents innovation in fighting lethal brain cancer and other solid tumors where there are limited options.
“My wife suffered from breast cancer, and she had a double mastectomy. In solid tumors, physicians not only remove the mass of the cancer, but they surgically remove the safety margin of the tissue around it in what’s called tumor debulking — in case there's any free cancer cells,” said Zarrabian.
“The problem with glioblastoma, unlike other solid tumors like breast cancer, is that you can't remove peripheral tissue because it's brain matter. If you remove an extra two or three centimeters of brain matter, you materially impact the patient's quality of life.”
The GBM AGILE advantage
Significantly, Kintara’s VAL-083 joined Bayer’s Regorafenib and Kazia’s Paxalisib as the three compounds currently in the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) study sponsored by the Global Coalition for Adaptive Research (GCAR).
During the first quarter ended March 31, 2021, Kintara achieved a major milestone as it started patient recruitment for its VAL-083 arm of the GBM AGILE trial.
VAL-083 is currently the only drug being evaluated in all three GBM patient subtypes of the trial— newly diagnosed methylated MGMT, newly diagnosed unmethylated MGMT, and recurrent.
The advantage of being included in GBM AGILE is that it has a regulatory buy-in with US Food and Drug Administration (FDA) support.
“We got an early Christmas present last year — I believe all patients did — with the FDA allowing Kintara to be in all three patient subsets,” said Zarrabian.
“It accelerates Phase 3 development times, while reducing expenses and gives us three separate shots on goal unique to VAL-083,” he added.
The Kintara boss noted that VAL-083’s evaluation in all three patient subtypes, may accelerate its time to pivotal trial completion and potential regulatory submission by up to 18 months.
Undoubtedly, platform trials can accelerate the time from discovery in the lab to implementation in the clinic.
“The GBM AGILE study is underway and rapidly enrolling patients. The study is anticipated to accelerate results in recurrent and newly diagnosed methylated and unmethylated patients while limiting total cost,” noted analysts at Zacks Investment Research.
Moreover, the analysts at Aegis Capital view VAL-083 as having “the potential to be a successor to TMZ in the treatment of GBM,” predicated on the outcome of the GBM AGILE study.
“We do envision a time where VAL-083 can replace temozolomide as the standard of care as a result of the GBM trial,” said Zarrabian.
In July this year, Kintara shared topline data results from the recurrent arm of its open-label, Phase 2 clinical study of VAL-083 being conducted at the MD Anderson Cancer Center in Houston.
The Phase 2 trial is a two-arm, biomarker-driven study testing VAL-083 in GBM patients, who have unmethylated MGMT. The recurrent arm of the study addressed patients who have been pre-treated with temozolomide prior to disease recurrence.
Median overall survival (mOS) for the 48 efficacy-evaluable patients at the 30 mg/m2/day dose level was 8 months. While this is not a head-to-head trial, historically, lomustine, which is the commonly used chemotherapy for these patients, has demonstrated an mOS of 7.2 months.
In September, Kintara is likely to see data from the MD Anderson newly diagnosed, unmethylated (adjuvant) Phase II study.
REM-001 is light activated
When Zarrabian took the reins of the company over three years ago, he wanted to diversify the company's assets.
“I started a two-and-a-half-year search to find a late-stage oncology product for patients who were underserved. We looked at well over 65 companies and assets until we ran into REM-001 which we acquired,” said Zarrabian.
In the case of REM-001, experts believe the targeted nature of how the sophisticated photosensitizer drug works avoids systemic exposure and addresses many of the shortcomings of surgery, chemotherapy, and radiotherapy for cutaneous metastatic breast cancer (CMBC) patients.
“Patients with CMBC, a highly morbid form of breast cancer, suffer bleeding, infectious and malodorous lesions on their chest wall, neck and back. It is unbearably painful — they need narcotics for pain control,” said Zarrabian.
REM-001 offers these patients hope where there are limited current therapies. The drug is genius in the way it works.
“REM-001 is infused in one day as an outpatient treatment. It takes about 30-40 minutes. The patient comes back 24 hours later, and the physician activates the drug using a laser light that penetrates the tissue at a certain depth and wavelength,” explains Zarrabian.
“That's why we call REM-001 light activated chemotherapy. There is compelling data that all the lesions that were treated within the time frame of the Phase 2 studies, showed an 80% complete response rate.”
With clinical effectiveness of 80% complete responses of CMBC evaluable lesions, and a robust safety database of around 1,100 patients across multiple indications, Kintara is advancing the REM-001 CMBC program to late-stage pivotal testing.
Undoubtedly, Kintara is punching above its weight on cancer innovation.
“I believe the company is grossly undervalued in the market based on having two late-stage clinical trials that have been fairly derisked given that each compound has been dosed to over 1,100 patients,” said Zarrabian.
“We are talking about a decade of human interactions, safety profile, and very large market opportunities,” he added.
VAL-083 is aimed at a roughly $800 million market, projected to grow to $1.4 billion in 2027, while REM-001 has a $500 million market opportunity.
Against this backdrop, Kintara which trades around $1.55 on the tech-laden Nasdaq has significant upside potential, according to analysts. Aegis Capital has rated Kintara a 'Buy,' while maintaining a $7 share target price.
Meanwhile, the analysts at Zacks Invesment Research said: “With a wealth of data available for VAL-083 and an unmet need in CMBC, we see Kintara as diversified and undervalued. We maintain our target price of $5.25 per share."
Kintara’s VAL-083 has received orphan designation from the US FDA and the European Committee for Orphan Medicinal Products.
Contact the author Uttara Choudhury at email@example.com
Follow her on Twitter: @UttaraProactive