On December 10, 2021 Caring Cross, a 501(c)(3) non-profit dedicated to accelerating the development of advanced medicines and enabling access to cures for all patients, everywhere, reported that Nature Communications has published a scientific manuscript highlighting research demonstrating the effectiveness of place-of-care manufacturing of anti-CD19 CAR T cells for treatment of B-cell malignancies (Press release, Caring Cross, DEC 10, 2021, View Source [SID1234597013]). Place-of-care manufacturing is defined as near the point of patient treatment allowing cell products to be produced and infused without need for cryopreservation.

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The manuscript, entitled, "Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients," reported that novel CD19-targeting CAR-T cells (CAR19-T cells) similarly manufactured using automation at separate sites in Cleveland, USA and Moscow, Russia achieved complete response rates of 73% in adult B-cell Lymphoma (NHL) and 89% in pediatric B-cell Acute Lymphocytic Leukemia (ALL), respectively. For NHL complete responders, the one-year survival rate was 92.9%, with a median duration of response yet to be reached. For ALL complete responders with a median follow-up of 17 months, the one-year survival rate was found to be 79.2% with a median duration of response of 10.2 months. Based on these findings, it was concluded that use of place-of-care manufactured CAR-T cell products results in clinical outcomes that are effective in the treatment of patients with B-cell malignancies.

Dr. Marcos de Lima, Director of Stem Cell Transplantation and Cellular Therapy at The Ohio State University Medical Center, and one of the lead investigators on the clinical trial, commented: "Our studies show that place-of-care manufacture of CAR-T cells results in a consistent cell product and produces effective clinical outcomes, despite being manufactured in two disparate clinical centers located in the US and Russia. We were able to make fresh CAR-T cells in as little as 8 days, which is very important for patients with rapidly progressing disease. We therefore conclude that place-of-care manufacture of CAR-T cells is a valid and valuable model for the manufacture and distribution of CAR-T cells among multiple clinical centers, and particularly important for patients with rapidly progressive, symptomatic lymphoma and ALL."

In addition to demonstrating that place-of-care manufacture of CAR-T cells results in a consistent cell product and effective clinical outcomes, the research team determined that fresh CAR19-T cells, which can only be manufactured at the place-of-care, reduce tumor burden faster in vivo in NSG mice than cryopreserved CAR19-T cells, immediately reducing the tumor burden, while frozen CAR19-T cells first permitted tumor growth before controlling growth. Moreover, the researchers found that place-of-care manufacture of CAR19-T cells resulted in a highly comparable CAR-T cell product composition between the multiple clinical centers and a low production failure rate, demonstrating the robustness of the manufacturing process.

Dr. Michael Maschan, Director of the Department of Hematopoietic Stem Cell Transplantation at the Dmitriy Rogachev National Center for Pediatric Hematology and Oncology in Moscow, Russia, commented: "Place-of-care manufacturing of CAR-T cells offers several advantages over centralized manufacturing, including reduced vein-to-vein time due to lack of transport to a centralized facility and the ability to infuse fresh and not necessarily cryopreserved products. Simplified logistics increases the flexibility to make decisions based upon patient disease status, for example split-dosing in the instance of high tumor burden. The high response rates we have seen in our clinical trials are outstanding considering that we were able to essentially treat all-comers due to the short manufacturing times of patient-derived CAR-T cell products, which are only possible when they are manufactured at the place-of-care. This has tremendous benefits for patients, particularly those with advance disease that need to be treated as soon as possible. We are delighted with the clinical results to date and look forward to future innovations to further improve patient outcomes."

Dr. Boro Dropulić, Executive Director of Caring Cross, commented: "This is the first study that definitively demonstrates the feasibility of place-of-care manufacturing of gene-modified cell products between muliple centers. We show that when the same device, materials, reagents and protocols are used to manufacture CAR-T cells, even between two disparate clinical centers, the gene-modified cell products are highly consistent with a low product failure rate. The clinical outcomes for patients were especially remarkable considering that almost all the patients enrolled were treated, even patients that otherwise would not be eligible due to their advanced disease, demonstrating the enormous value of this approach. Place-of-care manufacturing also offers the potential to dramatically reduce the cost of these transformational therapies to a fraction of their current cost due to obviating the need for transportation and the cost of multiple layers of quality and custodial assurance that are required for centralized manufactured CAR-T cell products. The next step will be to expand CAR-T cell clinical trials to include more clinical centers and support the development of regulatory pathways for the approval of CAR-T and other gene-modified cellular products that are manufactured at the place-of-care."

The full paper may be accessed via the Nature Communications website at View Source

On December 10, 2021 Race Oncology Limited ("Race") reported it has extended and expanded its collaborative cardio-protective research program for Zantrene (bisantrene dihydrochloride) with eminent cardiotoxicity researchers, Associate Professors Aaron Sverdlov and Doan Ngo, at The University of Newcastle (Press release, Race Oncology, DEC 10, 2021, View Source [SID1234596742]).

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This collaboration builds on the initial heart safety preclinical study (ASX announcement: 28 April 2021) and will explore the cardio-protective attributes of Zantrene in vitro when used in combination with an expanded panel of anti-cancer drugs known to damage the hearts of cancer patients, as well as to undertake animal studies.

Race revealed an updated Three Pillar Strategy at the 2021 AGM (ASX Announcement: 23 November 2021) building on the recent discovery that Zantrene is able to protect heart muscle cells from both anthracycline and carfilzomib-induced death while also better targeting cancer cells (ASX announcements: 22 November 2021 & 08 December 2021).

This strategically important collaboration will underpin a cardio-protective Phase 2b clinical trial in cancer patients at high risk of anthracycline-induced heart damage, which is expected to begin treating patients in late 2022.

"The success of our collaboration with Associate Professors Aaron Sverdlov and Doan Ngo has been exceptional to date. We all look forward to uncovering all the cardio-protection secrets Zantrene has to reveal."

Chief Scientific Officer, Dr Daniel Tillett
This program will cost $322K and start immediately, with results to be reported over the coming 12 months.

On December 10, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported a positive interim safety update from the investigator-sponsored, phase 2 IRENE trial in a poster presentation at the 2021 San Antonio Breast Cancer Symposium (SABCS) (Press release, Oncolytics Biotech, DEC 10, 2021, View Source [SID1234596760]).

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The IRENE trial is designed to evaluate the safety and efficacy of pelareorep in combination with Incyte’s anti-PD-1 checkpoint inhibitor retifanlimab for second- or third-line treatment of patients with metastatic triple-negative breast cancer (TNBC). Safety data from the trial show that the combination has been well-tolerated, as no safety concerns have been noted in any of the five patients enrolled in the trial at the time of reporting. The trial remains ongoing and will continue to enroll patients at the Rutgers Cancer Institute of New Jersey and the Ohio State University Comprehensive Cancer Center.

Mridula George, M.D., Medical Oncologist, Rutgers Cancer Institute of New Jersey, Assistant Professor of Medicine, Rutgers Robert Wood Johnson Medical School, and principal investigator of the trial commented, "Checkpoint inhibitors benefit only a minority of TNBC patients due to immunosuppressive tumor microenvironments (TMEs) and poor PD-L1 expression. Prior clinical studies have shown that pelareorep upregulates tumor PD-L1 expression and reverses immunosuppressive TMEs. These findings suggest that pelareorep can address a pressing unmet need in TNBC by synergizing with PD-1 inhibition to increase the proportion of patients responding to therapy. We look forward to evaluating this hypothesis through the IRENE study’s continued advancement and are pleased that the pelareorep-retifanlimab combination has been well-tolerated in each of the patients enrolled in the trial."

In addition to evaluating the safety and efficacy of pelareorep plus retifanlimab, IRENE is also designed to assess changes in PD-L1 expression and correlations between treatment outcomes and changes in peripheral blood T cell populations. This could provide a potential biomarker of pelareorep response that may enable the success of future registrational trials by allowing for the early identification of patients most likely to respond to therapy.

A copy of the SABCS poster titled, "IRENE study: Phase 2 study of Retifanlimab and the oncolytic virus pelareorep in metastatic triple negative breast cancer," will be available on the Posters & Publications page of Oncolytics’ website (LINK) following the conclusion of the symposium.

About IRENE
The IRENE (INCMGA00012 and the oncolytic virus pelareorep in metastatic triple-negative breast cancer) study is a single-arm, open-label, phase 2 study evaluating the combination of pelareorep and Incyte’s anti-PD-1 checkpoint inhibitor retifanlimab (INCMGA00012) for the second- or third-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer. The study will enroll 25 patients and is being conducted at the Rutgers Cancer Institute of New Jersey and The Ohio State University Comprehensive Cancer Center.

Study participants will receive pelareorep intravenously on days 1, 2, 15, and 16 of 28-day treatment cycles. Retifanlimab will be administered on day 3 of each cycle, with treatment cycles continuing until disease progression is observed. The co-primary endpoints of the study are safety and objective response rate. Secondary endpoints include progression-free survival, overall survival, and duration of response. Exploratory endpoints include peripheral T cell clonality and pre- vs. post-treatment change in tumor PD-L1 expression.

For more information on the IRENE study, refer to View Source

On December 10, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported Conditional Marketing Authorisation (CMA) of RYBREVANT ▼ (amivantamab) for the treatment of adult patients with advanced NSCLC with activating epidermal growth factor receptor (EGFR) exon 20 insertion mutations, after failure of platinum-based therapy (Press release, Johnson & Johnson, DEC 10, 2021, View Source; [SID1234596782]).1 Amivantamab is the first approved treatment in the European Union specifically targeting EGFR exon 20 insertion mutations for NSCLC.1,2,4

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"Patients with NSCLC harbouring EGFR exon 20 insertion mutations represent a specific population who have been underserved by current treatment options that are limited in both number and efficacy.5 The decision made by the European Commission represents an important milestone and recognises that amivantamab offers a new treatment specifically targeted for patients with this alteration," said Antonio Passaro, M.D., Ph.D, Medical Oncologist at the Division of Thoracic Oncology of the European Institute of Oncology in Milan, Italy.†

The CMA is based on results from the Phase 1 CHRYSALIS study, a multicentre, open-label, clinical study evaluating amivantamab as a monotherapy in patients after previous treatment with platinum-based therapy, which demonstrated efficacy and a generally well-tolerated safety profile.‡4,6 The investigator-assessed overall response rate was 37 percent (95 percent CI, 28% – 46%), with a median duration of response of 12.5 months (95 percent CI, 6.5 – 16.1) and 64 percent of patients having a duration of response greater than or equal to 6 months.4 These results were consistent with those reported by blinded independent central review assessment, which showed an overall response rate of 43 percent (34% – 53%), with a median duration of response of 10.8 months (95 percent CI, 6.9 – 15.0) and 55 percent of patients having a duration of response greater than or equal to 6 months.4

Analysis showed the median progression-free survival (time experienced without progression or death) was 8.3 months (95 percent CI, 6.5 – 10.9) and the median overall survival in patients treated with amivantamab was 22.8 months (95 percent CI, 14.6 – not reached).6

The most common adverse events (AEs) at all grades included rash (76 percent), infusion-related reactions (67 percent) and nail toxicity (47 percent), and these were predominantly Grade 1-2.4 Treatment-related discontinuations due to adverse events were seen in three percent of patients.4 Ninety-nine percent of infusion-related reactions occurred with the first infusions and rarely impacted the ability to continue with subsequent treatments (1.1 percent led to treatment discontinuation).4

"This marketing authorisation addresses a high unmet need by bringing a new treatment option to this patient population and their healthcare professionals for the first time in Europe. It is an important step towards our goal to deliver innovative therapies that will transform the trajectory of lung cancer," commented Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC.

Conditional marketing authorisation is the approval of a medicine that addresses unmet medical needs of patients based on less comprehensive data than normally required, where the benefit of immediate availability of the medicine outweighs the risk, and the applicant is able to provide comprehensive clinical data in the future.7 This CMA follows other recent approvals for amivantamab, including the U.S. Food and Drug Administration (FDA), who approved the treatment in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.8 Additional regulatory applications have been submitted and are being reviewed by other regulatory bodies worldwide.

"We are committed to changing the face of cancer care," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. "At Janssen, we’re striving to transform long-term patient outcomes and improve quality of life with the right treatment, for the right patient, at the right time."

† Dr Passaro has previously provided paid consultancy services for Janssen in relation to research and advisory boards. He has not been compensated for any media work.

‡ Results reported in the SmPC are from 114 patients with a median follow up of 12.5 months.4 Results reported in Park et al are from 81 patients and a median follow up of 9.7 months.6 Not all efficacy endpoints were reported in the SmPC.4,6

About Amivantamab
Amivantamab is a fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumours with activating and resistance EGFR mutations and MET mutations and amplifications, approved for patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations after failure of platinum-based therapy.1,9,10,11,12 Amivantamab is being studied in multiple clinical trials, including:13

the Phase 1/1b, CHRYSALIS-2 (NCT04077463) study assessing the combination of amivantamab and lazertinib in patients who have progressed after treatment with osimertinib and chemotherapy, as well as lazertinib as a monotherapy14
as first-line therapy in the Phase 3 MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib, a novel third-generation EGFR tyrosine kinase inhibitor (TKI), against osimertinib and against lazertinib alone in untreated advanced EGFR-mutated NSCLC15
the Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of lazertinib, amivantamab and carboplatin-pemetrexed vs. with carboplatin-pemetrexed in participants with locally advanced or metastatic EGFR Exon 19del or Exon 21 L858R substitution NSCLC after osimertinib failure16
the Phase 3 PAPILLON (NCT04538664)study assessing amivantamab in combination with carboplatin-pemetrexed vs carboplatin-pemetrexed for patients with advanced or metastatic EGFR-mutated NSCLC with exon 20 insertion mutations17
the Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab SC delivery with the aim to find effective solutions that positively impact patient management.18
About the CHRYSALIS Study
CHRYSALIS (NCT02609776) is an open-label, multicentre, first-in-human Phase 1 study to evaluate the safety, pharmacokinetics and preliminary efficacy of amivantamab as a monotherapy, in combinations with lazertinib and in combination with platinum-based chemotherapy, in patients with advanced NSCLC with various EGFR mutations.3 In the study, investigators assessed efficacy using overall response rate per Response Evaluation Criteria in Solid Tumours Version 1.1* (RECIST v1.1), clinical benefit rate, median duration of response and median progression-free survival, as well as the safety profile of amivantamab.3,19

The study will enrol 780 patients with advanced NSCLC.3 The study consists of two parts: the first consists of amivantamab monotherapy and combination dose escalations, and the second consists of amivantamab monotherapy and combination dose expansions.3

The first cohort of participants received intravenous infusions of amivantamab as monotherapy.3

*RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumours, which is a standard way to measure how well solid tumours respond to treatment and is based on whether tumours shrink, stay the same or get bigger.3

About Non-Small Cell Lung Cancer (NSCLC)
In Europe, it is estimated that 477,534 patients were diagnosed with lung cancer in 2020, with around 85 percent diagnosed with NSCLC.20,21 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.20

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.21 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.22 EGFR mutations are present in 16 to 19 percent of Caucasian patients with NSCLC and present in 37 to 41 percent of Asian patients who have NSCLC adenocarcinoma.23 The five-year survival rate for all people with metastatic NSCLC and EGFR mutations who are treated with EGFR TKIs is less than 20 percent.24 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of 8 percent in the frontline setting, which is worse than patients with EGFR exon 19 deletions or L858R mutations, who have a real-world five-year OS of 19 percent.25

On December 9, 2021 LianBio (Nasdaq: LIAN), a biotechnology company dedicated to bringing innovative medicines to patients in China and other major Asian markets, reported financial results for the third quarter ended September 30, 2021 (Press release, LianBio, DEC 9, 2021, View Source [SID1234596662]).

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"Over the past several months, the LianBio team has achieved multiple meaningful milestones, including initiating our first clinical trial, completing dosing in our first PK study and successfully completing our initial public offering," said Yizhe Wang, Ph.D., Chief Executive Officer of LianBio. "In the year ahead, we intend to continue to advance our pipeline of innovative medicines and expect to initiate four pivotal studies to support regulatory approval in our territories. I’m confident we have the leadership and expertise at hand, as well as the capital resources necessary to deliver on our commitment to bring transformative medicines to patients across Asia."

Recent Business Highlights and Clinical Development Updates:

Initiated and completed enrollment and dosing in pharmacokinetic study of mavacamten

In November, LianBio initiated and completed enrollment and dosing in a pharmacokinetic (PK) study of mavacamten in healthy Chinese volunteers.
Initiated Phase 2a clinical trial of infigratinib in gastric cancer and other advanced solid tumors

In August, LianBio announced that the first patient was dosed in a Phase 2a clinical trial of infigratinib in locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with fibroblast growth factor receptor-2 (FGFR2) gene amplification and other advanced solid tumors with FGFR genomic alterations.
Appointed two independent directors to LianBio Board of Directors

In October, LianBio appointed Jesse Wu to the Company’s Board of Directors. Mr. Wu is the former Chairman of Johnson & Johnson China.

In October, LianBio appointed Susan Silbermann to the Company’s Board of Directors. Ms. Silbermann is the former Global President, Emerging Markets at Pfizer.
Strengthened LianBio leadership team with key China-based hires

In October, LianBio appointed Michael Humphries, MBBS as Chief Scientific Advisor to guide the Company’s research and development (R&D) strategy, advance the Company’s pipeline, and lead assessment of new in-licensing opportunities.

In August, LianBio appointed Pascal Qian as China General Manager to build out the Company’s operations and commercial infrastructure.
Completed Initial Public Offering

In November, LianBio completed an initial public offering (IPO) of its ordinary shares through the sale and issuance of 20,312,500 American Depositary Shares (ADSs) at a public offering price of $16.00 per ADS. Following the close of the IPO, pursuant to the partial exercise of their option to purchase additional ADSs, the underwriters purchased an additional 593,616 ADSs at the IPO price of $16.00 per ADS.

LianBio received gross proceeds of $334.5 million in connection with the IPO and subsequent exercise of the underwriters’ option and aggregate net proceeds of $311.1 million after deducting underwriting discounts and commissions.
2022 Key Anticipated Milestones

Mavacamten
Bristol Myers Squibb (BMS)-partnered cardiac myosin inhibitor in development for the treatment of hypertrophic cardiomyopathy and certain forms of heart failure

LianBio expects to initiate the Phase 3 EXPLORER-CN trial of mavacamten in Chinese patients with obstructive hypertrophic cardiomyopathy in the first quarter of 2022 to support regulatory approval in China.
LianBio’s partner BMS has announced a Prescription Drug User Fee Act (PDUFA) target action date of April 28, 2022 for the Company’s New Drug Application to the U.S. Food and Drug Administration (FDA) for mavacamten for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
TP-03
Tarsus Pharmaceuticals-partnered GABA-Cl channel blocker in development for the treatment of Demodex blepharitis (DB) and meibomian gland disease

LianBio expects to initiate a Phase 3 trial of TP-03 in Chinese patients with DB in the second half of 2022 to support regulatory approval in China.
LianBio’s partner Tarsus has announced that the Company expects to report topline data in the first quarter of 2022 from the ongoing Phase 3 Saturn-2 trial of TP-03 in DB patients.
NBTXR3
Nanobiotix-partnered radioenhancer in development for multiple solid tumor indications

LianBio expects to begin dosing Chinese patients in Nanobiotix’s planned global pivotal Phase 3 trial of NBTXR3 for the treatment of locally advanced head and neck squamous cell carcinoma in elderly patients ineligible for cisplatin in the second half of 2022.
LYR-210
Lyra Therapeutics-partnered anti-inflammatory implantable drug matrix in development for the treatment of surgically-naïve, medically refractory chronic rhinosinusitis

LianBio expects to begin dosing Chinese patients in Lyra’s planned global pivotal Phase 3 trial of LYR-210 for the treatment of surgically naïve chronic rhinosinusitis in the second half of 2022.
Third Quarter 2021 Financial Results:

Research & Development Expenses

R&D expenses were $4.7 million for the three months ended September 30, 2021, as compared to $116.9 million for the three months ended September 30, 2020. For the three months ended September 30, 2021, research and development cost was primarily attributable to $1.9 million in personnel-related expenses and $2.1 million in professional fees for development activities to support clinical trials.

General & Administrative Expenses

G&A expenses were $8.9 million for the three months ended September 30, 2021, as compared to $2.1 million for the three months ended September 30, 2020. The increase was primarily attributable to increases in payroll and personnel-related expenses (including share-based compensation expense) for increased employee headcount and increases in legal service costs, consulting costs and accounting services.

Net Loss

Net loss was $13.1 million for the three months ended September 30, 2021, or a net loss per share of $0.63, as compared to a net loss of $120.2 million for the three months ended September 30, 2020, or a net loss per share of $11.71.

Cash and Cash Equivalents

Cash and cash equivalents were $109.0 million as of September 30, 2021, which excludes the net proceeds of $311.1 million from the Company’s initial public offering, as compared to $254.4 million as of December 31, 2020. The Company expects its current cash and cash equivalents, inclusive of the IPO net proceeds subsequently received in November 2021, will be sufficient to fund its operating expenses and capital expenditure requirements through 2023.