On October 19, 2022 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported its Appendix 4C quarterly cash flow statement and accompanying Activities Report for the quarter ended 30 September 2022 (Q3 2022) (Press release, Telix Pharmaceuticals, OCT 19, 2022, View Source [SID1234622201]). All figures are in AUD$ unless otherwise stated.[1] All figures are provided on an unaudited basis.
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Financial Summary
Telix reports total revenue of $55.3 million from global sales of Illuccix, up 168% on the previous quarter ($20.6 million, Q2 2022)
U.S. sales of Illuccix up 178% to $53.7 million (US$36.4 million) in second quarter of commercial sales ($19.3 million, Q2 2022)
Cash balance of $117.1 million; provides 21 quarters of cash runway (based on Q3 2022 burn rate)
Net operating cash outflow reduced by $20.5 million to $5.3 million, a significant reduction on the prior quarter ($25.8 million net operating cash outflow). Key factors impacting this improvement are:
Customer receipts of $44.5 million, up from $5.4 million in the previous quarter, reflecting growth in commercial sales
Q3 2022 expenditure to support commercial operations reflecting normalised operations, following one-off launch costs incurred in H1 2022
Ongoing cost-control of research and development (R&D) expenditure, aligned with product earnings growth
Capital expenditure included $1.7 million in build-out costs related to Telix’s manufacturing facility in Brussels South (Seneffe)
Commercial Activity Report
U.S. commercial update
In Q3 2022, the second quarter of commercial sales, Telix generated $53.7 million (US$36.4 million) revenue from sales of its prostate cancer imaging agent, Illuccix (kit for the preparation of gallium-68 (68Ga) gozetotide (also known as PSMA-11) injection). This represents a 178% increase on the previous quarter ($19.3 million, Q2 2022). Sales have increased steadily month on month since U.S. reimbursement – HCPCS[2] code and transitional pass-through payment status – became effective on 1 July 2022. Doses were via Telix’s distribution network, currently consisting of 179 radiopharmacies.
Mr. Kevin Richardson, CEO Telix Americas said, "We are pleased with sales momentum since the U.S. launch. Sales have continued to increase each month, and we have continued to gather pace since reimbursement came into effect on 1 July. We have quickly built a diversified customer base and continue to add new sites. Notably, the commencement of pass-through in July has opened up access to more hospital outpatient accounts, including some of the major academic centres in the U.S. that recognise Illuccix’s differentiation in terms of scheduling flexibility and clinical workflow."
Illuccix (TLX591-CDx)[3] worldwide revenue
A total of $55.3 million in revenue was generated from sales of TLX591-CDx during the quarter. Of this, $1.6 million was generated from rest of world sales, predominantly from pre-commercial sales,[4] primarily in Europe and the United Kingdom.
Commercial sales of Illuccix in Australia[5] and New Zealand[6] commenced in September 2022.
Net operating cash outflow
Net operating cash outflow was $5.3 million, reduced from $25.8 million in the previous quarter. This improvement was driven by an increase in customer receipts, in line with the growth in commercial sales, and a continued focus on cost management.
A total of $44.5 million in customer receipts was generated from sales of Illuccix. Net operating cash outflow in Q3 2022 is largely reflective of normalised operations, noting that in H1 2022 one-off costs were incurred for commercial launch in the U.S..
Product manufacturing and operating costs increased to $10.7 million, from $8.6 million in Q2 2022, due to a higher volume of sales, but have reduced as an overall percentage of sales. It should be noted that ongoing manufacturing costs pertain to building medium-term inventory to service both U.S. and global customers.
R&D expenditure remained well controlled, with $16.3 million invested in R&D, manufacturing and clinical development activities, compared to $17.4 million in Q2 2022.
Illuccix (TLX591-CDx) global regulatory and reimbursement updates
During the quarter, the Company announced it had withdrawn its marketing authorisation application (MAA) in Europe.[7] In the late stages of the review the Danish Medicines Agency (DKMA) in consultation with other European regulatory authorities, requested additional Chemistry, Manufacturing and Control (CMC) data. These requests could not be reasonably delivered within the prescribed review timeframe. The Company is assessing alternative regulatory options available for the most streamlined route to approval with a revised submission and will provide an update on anticipated timings when this assessment has been completed.
Subsequent to the quarter (14 October 2022), the Company announced that Health Canada had approved Illuccix for use in staging and re-staging intermediate and high-risk prostate cancer and localising tumour tissue in recurrent prostate cancer.[8] Illuccix is the first PSMA PET[9] imaging agent to be granted regulatory approval in Canada. This is the third key market regulatory approval for Illuccix. Illuccix will be made available in Canada to physicians and eligible patients through Telix’s partner, Isologic Innovative Radiopharmaceuticals, whose distribution network services 265 hospitals and clinics nationwide.
Also subsequent to the quarter (17 October 2022) the Company announced that Telix and its partner Grand Pharmaceutical Group Limited (Grand Pharma), had received approval from the National Medical Products Administration (NMPA) Center for Drug Evaluation (CDE) to commence a pivotal Phase III registration study that will bridge to the United States Food and Drug Administration (FDA) approval of Illuccix.[10] The study is expected to commence in Q1 2023.
Marketing authorisation applications for TLX591-CDx are under review and progressing in Brazil and South Korea. Telix currently has a temporary use (pre-approval) authorisation in the Czech Republic and Brazil.
Clinical Programs Update
Telix continues to progress its clinical pipeline, with a core focus on prostate cancer, kidney cancer, brain cancer (glioblastoma) and rare diseases (bone marrow conditioning). The Company has more than 20 clinical trials underway, including collaborative investigator-sponsored studies. Notable updates are included in this section of the activities report.
Renal cancer / CAIX program
The Company expects to report top line data from the ZIRCON Phase III study of TLX250-CDx (89Zr-DFO-girentuximab), an investigational product for the imaging of clear cell renal cell carcinoma (ccRCC) with positron emission tomography (PET) around the first week of November 2022.
The Company is preparing to launch an Expanded Access Program (EAP) to enable eligible patients to access TLX250- CDx to address unmet need and requests for access under the healthcare professional responsibility prior to marketing authorisation. This is in accordance with Telix’s Compassionate Use Policy[11] subject to jurisdictional regulatory requirements in selected countries, dependent on local regulatory requirements.
Subsequent to quarter (17 October 2022), Telix announced a collaborative development and reseller agreement with GE Healthcare to supply two of its PET imaging radiotracers (TLX250-CDx and [18F]-FLac (18F-3-fluoro-2-hydroxypropionate)) for use in third party pharmaceutical company clinical research and development activities.[12] The agreement will see these two investigational agents added to GE Healthcare’s immuno-diagnostic portfolio. GE Healthcare’s Pharmaceutical Diagnostics business is an established global supplier of PET imaging tracers to the global clinical research market. This partnership will enable these investigational imaging agents to be used more widely in third-party clinical trials, separate to Telix’s commercialisation of TLX250-CDx.
The Company also reported that the Chinese National Medical Products Administration (NMPA) Center for Drug Evaluation (CDE) approved a pivotal Phase III registration study that will bridge to Telix’s global Phase III ZIRCON trial.[13] The bridging study is required to provide "supplementary" data obtained in a Chinese population to establish that the diagnostic efficacy of this investigational product is equivalent in Chinese and Western populations. A dosimetry study enrolling 10 patients will precede the multi-centre Phase III bridging study, which is expected to enrol 100 patients. The investigational new drug (IND) application was submitted by Telix’s partner in the Greater China region, Grand Pharma.
TLX250-CDx potential for indication expansion
Positive preliminary data from two separate investigator-initiated studies in triple negative breast cancer (TNBC) ( OPALESCENCE study) and non-muscle-invasive bladder cancer (NMIBC) (PERTINENCE study), were presented at the European Association of Nuclear Medicine (EANM) Annual Congress held in Barcelona, Spain from 15-19 October 2022.[14] These studies evaluating carbonic anhydrase IX (CAIX) expression in cancers other than ccRCC, support Telix’s goal to rapidly expand the CAIX program into other indications beyond kidney cancer.
OPALESCENCE (NCT04758780) a Phase II study of TLX250-CDx is investigating how carbonic anhydrase IX (CAIX) targeting imaging with PET can be utilised for the diagnosis and staging of TNBC and its potential as a therapeutic target in this patient population. Preliminary data demonstrates the feasibility of girentuximab to target CAIX expression in TNBC. Early results suggest potential for girentuximab as an imaging agent and therapeutic in this poor prognosis disease: 83% patient lesions had a CAIX strong expression allowing TLX250-CDX immunoPET detection, showing promise for further investigation.
Based on these results, TLX250-CDx is an attractive novel investigative targeting agent for TNBC and potential alternative to biopsy and immunohistochemistry (IHC) for staging metastatic disease and targeted radioligand therapy. Should the targeting properties of this PET/CT imaging tracer be established in TNBC, Telix’s intention is to broaden future applications for lutetium-177 and actinium-225 based CAIX therapies.
PERTINENCE (NCT04897763) is an open-label, proof of concept study to evaluate safety profile, biodistribution and tumour targeting properties of TLX250-CDx given directly into the bladder in patients with NMIBC and to establish CAIX as a potential therapeutic target in this condition. Preliminary data from this feasibility, dosimetry and imaging study at Institut de Cancérologie de l’Ouest (ICO), shows encouraging tumour targeting and biodistribution with TLX250-CDx, and no systemic distribution of radiation. Based on these results, Telix’s partner ATONCO intends to progress TLX250 labelled with the alpha-emitter astatine-211 (211At) into a first-in-human Phase I targeted alpha therapy (TAT) study.
Prostate cancer / PSMA program
Telix’s PSMA-targeting ProstACT therapeutic program is evaluating the efficacy of Telix’s lutetium-177 (177Lu)-labelled therapeutic antibody (TLX591) in various stages of prostate cancer, from first recurrence to advanced metastatic disease.[15]
The ProstACT SELECT study, a "theranostic" (imaging and therapy) Phase I radiogenomics study to demonstrate the utility of Illuccix imaging to select TLX591 patients for therapy, continues to recruit well. During the quarter, a first patient was enrolled in the Phase II ProstACT TARGET study of TLX591, in patients experiencing a first recurrence of prostate-specific antigen (PSA) after initial therapy for prostate cancer.[16] The Company is progressing its manufacturing scale up and global regulatory submissions for ProstACT GLOBAL Phase III study.
The NOBLE (Nobody Left Behind) Registry continues to collect clinical data to inform the development of TLX599-CDx (99mTc-iPSMA), an investigational prostate cancer imaging agent that targets PSMA using single photon emission computed tomography (SPECT) imaging.[17] SPECT is the predominant imaging modality in many countries, including remote and rural regions. The NOBLE Registry aims to accelerate global access to advanced prostate cancer imaging where PET is not an option and is now active across eight sites globally.[18] The NOBLE Registry is funded in collaboration with the Oncidium Foundation. During the quarter two new sites in Indonesia and South Africa dosed their first patients.
Glioblastoma (brain cancer) / LAT-1 program
During the quarter Telix reported the final results from the IPAX-1 Ph I/II study of TLX101 therapy (4-L-[ 131I] iodo- phenylalanine, or 131I-IPA) in combination with external beam radiation therapy (EBRT) in recurrent glioblastoma multiforme (GBM).[19] The primary objective of the IPAX-1 study, which enrolled 10 patients (of whom 9 received the full study treatment dosing of ~2GBq (2000 MBq) was to evaluate the safety and tolerability profile of intravenous 131I-IPA administered concurrently with second line EBRT in patients with recurrent GBM.
Final data from the post-study follow-up period confirms the study has met its primary objective, demonstrating the safety and tolerability profile of TLX101 at the dosing range tested. The study also delivered encouraging preliminary efficacy data for further evaluation, demonstrating a median overall survival (OS) of 13 months from the initiation of treatment in the recurring setting, or 23 months from initial diagnosis. Given that GBM has a median survival from initial diagnosis of 12-15 months, the overall survival improvement trend seen in this patient population clearly warrants further evaluation in a larger patient population.
Telix has initiated a Phase I study, IPAX-2, to confirm safety of TLX101 as a front-line therapy in combination with standard of care treatment, ahead of progressing to a label-indicating Phase II study. In parallel, TLX101 is being investigated in the recurrent setting in the investigator-initiated IPAX-Linz Phase II study.[20]
Research, Innovation and Manufacturing
Construction continues at the site at Brussels South, with the process of clean room construction and hot cell installation for nine good manufacturing practice (GMP) manufacturing lines for isotope production now underway.
During the quarter, Telix was part of a consortium awarded a $4.8 million Australian Research Council (ARC) grant to establish a new Industrial Transformation Research Program (ITRP) Hub as part of a consortium of applicants led by The University of Queensland (UQ).[21] The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science.
Payments to Related Parties
Telix confirms that payments noted under section 6.1 of the Appendix 4C include payments of $0.4 million to ABX-CRO advanced pharmaceutical services (of which Non-Executive Director Dr. Andreas Kluge is Managing Director) for the provision of clinical and analytical services for the Company’s development programs. Payments of $0.3 million to Directors were for Director fees and Managing Director salary.