On September 13, 2023 Starpharma (ASX: SPL, OTCQX: SPHRY) reported that positive interim results from its Phase 1/2 clinical trial of DEP irinotecan will be presented at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper), National Cancer Institute (NCI) and European Organisation for Research and Treatment of Cancer (EORTC) AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, US, from 11 to 15 October 2023 (Press release, Starpharma, SEP 13, 2023, View Source;mc_eid=bf52dd3418 [SID1234635114]).

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DEP irinotecan is a novel, patented, nanoparticle formulation of SN38, the active metabolite of the widely used anti-cancer drug, irinotecan (marketed as Camptosar), developed using Starpharma’s proprietary DEP technology.

The DEP irinotecan data being presented include encouraging durable signs of efficacy combined with excellent tolerability not only in the irinotecan-approved indication of advanced metastatic colorectal cancer (CRC), but also in platinum-resistant/refractory ovarian cancer, which represents a new market opportunity. These positive results, including prolonged disease control and significant tumour shrinkage, have been achieved in heavily pre-treated patients who have received an average of up to 6 prior treatment regimens and 31 cycles and exhausted all available treatment options.

The data will be presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) by Dr Jenny Liu, MD, PhD, FRACP, Medical Oncologist and Principal Investigator at the Kinghorn Cancer Centre, St Vincent’s Hospital in Sydney, who commented on the positive results:

"The results of the DEP irinotecan trial to date have been very promising for patients with advanced colorectal cancer who have exhausted standard treatment options, with prolonged responses and excellent tolerance of the product, including in patients who could not previously tolerate standard irinotecan or had failed prior therapy.

"Our experience in treating more than 20 patients on the trial to date have shown promisingly low rates of severe gastrointestinal adverse events and absence of cholinergic toxicity, which are both common and problematic side effects of standard irinotecan therapy. I am also getting consistent feedback from several patients in the trial that they far prefer DEP irinotecan plus 5-FU/LV compared to the standard FOLFIRI regimen, which uses conventional irinotecan.

"In this heavily pre-treated group of CRC patients, prolonged disease control seen with DEP irinotecan is an excellent outcome and a significant clinical benefit and warrants ongoing development."

Dr Natalie Cook, MBChB, MRCP, PhD, the Principal Investigator of the study, a Medical Oncologist and Clinical Lead for the Manchester Experimental Cancer Medicine Centre at the Christie Hospital and University of Manchester in the UK, commented:

"I am impressed with the data on Starpharma’s novel dendrimer formulation of the irinotecan active metabolite, SN38. In our patients, DEP irinotecan has shown excellent tolerability and very encouraging efficacy.

"Compared to conventional irinotecan, tolerability for DEP irinotecan is much improved. Based on the trial data, I believe DEP irinotecan represents a well-tolerated and promising treatment alternative for patients with colorectal cancer, and potentially others, including platinum-resistant ovarian cancer."

DEP irinotecan interim clinical results in colorectal cancer1 (CRC)

Advanced metastatic CRC patients enrolled in the monotherapy cohort (N=38) were heavily pre-treated, having received an average of 4 prior treatment regimens and 31 cycles before entering the study. These patients, aged 35 to 78 years, had exhausted all available treatment options. All but one (97%) of the patients had progressed after prior treatment with conventional irinotecan (up to 4 lines) either as monotherapy or in combination. Despite this heavy pre-treatment, DEP irinotecan monotherapy achieved durable efficacy responses (stable disease [SD] and tumour shrinkage) for up to 72 weeks (~16 months), with disease control in 48% (15/31) of evaluable2 patients.

DEP irinotecan is also being evaluated in combination with 5-fluorouracil (5-FU) and leucovorin (LV), which is a standard irinotecan combination regimen used in the treatment of CRC known as "FOLFIRI". In this combination cohort, there are five evaluable CRC patients thus far, with treatment and enrolment ongoing. The DCR3 achieved in this cohort is 100%, with an ORR4 of 20%. For comparison, published data in advanced CRC patients for conventional irinotecan plus 5-FU/LV (FOLFIRI) as second-line therapy (i.e., in patients less heavily pre-treated than in the current study) reported an ORR of 4%5. In the DEP irinotecan combination cohort, clinicians have reported significant clinical benefit in these heavily pre-treated patients, including durable responses for up to 27 weeks (SD and partial response [PR]) and very good tolerability. Multiple patients have also provided positive feedback about the improved quality of life experienced with DEP irinotecan compared to conventional irinotecan therapy.

DEP irinotecan interim clinical results in platinum-resistant/refractory ovarian cancer

In addition to the positive results in CRC patients, DEP irinotecan demonstrated excellent responses in patients with advanced metastatic ovarian cancer (N=23). These patients were very heavily pre-treated, with an average of ~6 prior treatment regimens and 30 cycles before treatment with DEP irinotecan. Furthermore, all patients’ cancer was resistant or refractory to platinum-based therapies, which are the standard-of-care in ovarian cancer, and patients had exhausted all available standard-of-care treatment options.

DEP irinotecan monotherapy achieved a DCR of 100% and an ORR of 29% in ovarian cancer patients dosed every 2 weeks (Q2W). The DCR achieved in all ovarian cancer patients (Q2W and Q3W) is 72%, with several patients continuing to receive treatment and experiencing clinical benefit.

DEP Irinotecan Response Rates in Platinum-Resistant/Refractory Ovarian Cancer Patients

Endpoint

DEP Irinotecan Dosing Regimen

Once every 2 weeks (Q2W)

(N=7)

Q2W + Once every 3 weeks (Q3W)

(N=18)

DCR

100%

72.2%

ORR

28.6%

16.7%

DCR, disease control rate; ORR, objective response rate

Responses to DEP irinotecan treatment in these heavily pre-treated ovarian cancer patients have included tumour shrinkage of up to 60%, response durations of up to 36 weeks, and tumour biomarker reductions of up to 98% in more than 75% of patients. Clinical benefits reported by investigators in the study included complete resolution of a patient’s debilitating tumour-related ascites and pleural effusion.

DEP irinotecan’s impressive ORR of 29% in these heavily pre-treated patients compares favourably to standard-of-care single-agent therapies for platinum-resistant ovarian cancer, including paclitaxel (Taxol), topotecan (Hycamtin), gemcitabine (Gemzar) or pegylated liposomal doxorubicin (Caelyx), which report ORRs ranging from ~9 to 16%6,7,8.

This cohort of patients with platinum-resistant/refractory ovarian cancer represents a significant unmet medical need and a potential expansion of the current market for irinotecan, given conventional irinotecan is not approved for the treatment of ovarian cancer, either alone or in combination.

The anti-tumour activity of DEP irinotecan, including prolonged disease control in heavily pre-treated CRC and ovarian cancer patients, is encouraging as it demonstrates the promising clinical utility of DEP irinotecan and its potential for application in colorectal and platinum-resistant/refractory ovarian cancers.

In addition to CRC and ovarian cancer, DEP irinotecan has also shown encouraging efficacy signals in pancreatic, gastrointestinal and breast cancer patients.

Safety and tolerability of DEP irinotecan

Throughout the study, DEP irinotecan therapy has been very well tolerated, with significantly fewer severe gastrointestinal treatment-related adverse events (TRAEs) reported compared to published data on conventional irinotecan.

Importantly, DEP irinotecan therapy resulted in no reports of severe or life-threatening (≥ grade 3) diarrhoea across ~100 patients enrolled in the study. This result is a significant improvement in the side effect profile when compared to conventional irinotecan (Camptosar) treatment, which is associated with severe or life-threatening diarrhoea in more than 20% of patients9. Irinotecan-induced diarrhoea is frequently associated with the discontinuation of treatment and hospitalisation, and can have potentially fatal outcomes.

In patients treated with DEP irinotecan, either alone or in combination with 5-FU/LV, there have also been no reports of cholinergic syndrome, which occurs in approximately 47% of patients treated with conventional irinotecan8. This problematic adverse event involves symptoms such as acute diarrhoea, slow heartbeat, low blood pressure, increased salivation and tears, blurred vision, excessive sweating, flushing, and abdominal cramping.

TRAEs for DEP irinotecan have been mostly mild/moderate and include nausea, vomiting, fatigue, hair loss, and bone marrow toxicity (myelosuppression). Importantly, there have also been no immune-mediated adverse events with DEP irinotecan, making it suitable for combination with immune-oncology agents. In addition, no new adverse events were observed with DEP irinotecan compared to conventional irinotecan.

Gastrointestinal Treatment-Related Adverse Events (TRAE) in CRC Patients Treated with DEP Irinotecan Monotherapy* versus Camptosar^ (Conventional Irinotecan)

Treatment

DEP Irinotecan

Camptosar

DEP Irinotecan

Camptosar

TRAE

Grade 3/4

Grade 3/4

All Grades

All Grades

Diarrhea

0%

22%

33.3%

84%

Nausea

2.6%

12.7%

71.8%

70%

Vomiting

0%

14%

30.8%

62%

*N=38; ^N=316

Dr Jackie Fairley, CEO at Starpharma, said:

"We are pleased to report positive results for DEP irinotecan, which has shown promising activity and significantly improved tolerability in advanced colorectal cancer and ovarian cancer. The conference in October is a great opportunity to showcase both DEP irinotecan and the DEP platform more broadly.

"Starpharma has received consistent feedback from patients and clinicians indicating that DEP irinotecan represents a better-tolerated treatment option than conventional irinotecan regimens, which are the mainstay chemotherapeutics for colorectal cancer. Advanced colorectal and ovarian cancers both represent significant unmet medical needs. According to the World Health Organisation (WHO), an increase of about 70% in colorectal cancers globally is expected by 2030."

Recruitment into the DEP irinotecan trial has been completed for the monotherapy arm, with a small number of ovarian cancer patients ongoing. Recruitment of colorectal cancer patients into the combination arm is approaching completion and is expected to complete during September 2023, with top-line Phase 2 results to be released following completion of patient treatment and data analyses. While finalising the enrolment, treatment and analyses of clinical trial results, Starpharma is also engaging in commercial partnership discussions for DEP irinotecan and other DEP assets.

NOTES

About DEP irinotecan

DEP irinotecan is a novel, patented, nanoparticle formulation of SN38, the active metabolite of the widely used anti-cancer drug, irinotecan (marketed as Camptosar), delivered using Starpharma’s proprietary DEP technology. Camptosar and all generic forms of conventional irinotecan carry ‘black box’ warnings mandated by the US Food and Drug Administration (FDA) for both neutropenia and severe diarrhoea, which can be dose-limiting and life-threatening. DEP irinotecan has not resulted in severe diarrhoea in Phase 2 studies. DEP irinotecan has patent filings to 2039 and up to an additional five years.

The severe diarrhoea caused by conventional irinotecan results from the production of toxic metabolites during the liver metabolism of irinotecan to SN38. DEP irinotecan was designed to eliminate the need for liver metabolism, thereby avoiding the production of toxic metabolites.

About Starpharma’s DEP irinotecan Phase 2 clinical trial

Starpharma is evaluating DEP irinotecan as both a monotherapy and in combination with 5-fluorouracil (5-FU) and leucovorin (LV), which is a standard irinotecan combination regimen used in the treatment of CRC known as "FOLFIRI". The Phase 2 DEP irinotecan trial is being conducted at multiple sites, including Guy’s Hospital in London, Beatson Cancer Centre in Glasgow, Imperial College London, and the Kinghorn Cancer Centre in Sydney.

Clinical and commercial opportunity for DEP irinotecan

The global colorectal cancer drugs market was valued at ~US$14 billion in 2023 and is forecast to reach more than US$16 billion by 202710.

Camptosar and generic forms of conventional irinotecan are standard-of-care treatments for advanced CRC, with Pfizer’s Camptosar achieving peak sales of ~US$1.1 billion. CRC accounts for approximately 10% of all new cancer diagnoses and is the second leading cause of cancer, affecting more than 1 million people annually, and is the fourth leading cause of cancer-related death.

CRC incidence is increasing markedly among younger age groups, with rates of colon cancer more than doubling in adults aged 20 to 54 since the 1990s. Studies have shown that, compared with adults born around 1950, those born around 1990 have double the risk of colon cancer and quadruple the risk of rectal cancer11.

On September 12, 2023 Carina Biotech, a cell therapy immuno-oncology company, reported that it will be presenting at the 7th Annual Cell and Gene Therapy World Asia 2023 Conference in Singapore on 14-15 September (Press release, Carina Biotech, SEP 13, 2023, View Source;utm_medium=rss&utm_campaign=press-release-carina-to-present-at-7th-annual-cell-and-gene-therapy-world-asia-2023-conference [SID1234635096]).

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The conference attracts more than 300 cell and gene therapy professionals from over 150 companies. The conference is an opportunity for Asia-Pacific companies to connect with leading global cell and gene therapy companies and big pharma in networking and speaking sessions.

Chief Executive Officer Dr Deborah Rathjen will be presenting Carina’s success in taking its lead CAR-T asset CNA3103 from preclinical development through to clinical trials. Dr Rathjen will also be participating in a leadership panel discussion to share her extensive experience in biotech and pharmaceutical industries locally and internationally.

On September 13, 2023 Apmonia Therapeutics, a biotechnology company developing new therapeutic strategies aimed at reprogramming the tumor microenvironment by targeting elements of the extracellular matrix, reported the signature of a new licensing agreement and the launch of a co-development program with SATT Nord (technology transfer office of universities in the "North of France) (Press release, SATT South-East, SEP 13, 2023, View Source [SID1234635095]). Apmonia Therapeutics has obtained exclusive worldwide rights on LBC peptides, now also referred as AP-04, a program currently in preclinical development with the potential to generate {first-in-class candidates for the treatment of various solid tumors, notably triple-negative breast cancer.

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AP-04 targets pro-cathepsin-D, a protein overexpressed in various cancers (breast, ovarian, lung, etc.), inhibiting its interaction with LRP-1 membrane receptor. Through this unique mechanism of action, ‘AP-04 blocks the effect of pro-cathepsin-D/LRP-1 interaction on fibroblast proliferation and its deleterious role in a tumoral context.

Initiated within a CNRS/University of Reims Champagne-Ardenne joint research unit (MEDyC), this program is the fruit of a co-development program lasting over a year between Apmonia Therapeutics {and SATT Nord, at the end of which a patent was filed. Apmonia Therapeutics and SATT Nord now plan ‘to consolidate and extend the preclinical proof-of-concept of AP-04 before its entry into regulatory development, a key step prior to the transition into clinical development.

"We are delighted with the development of Apmonia Therapeutics, since SATT Nord has already signed 4 first licensing agreement in 2019 with them, also with the relationship of trust, built over the long term, which is reflected in a co-development approach" says Fabrice Lefebvre, CEO of SATT Nord, adding, "We are delighted that a new asset resulting from academic research within the scope of SATT ‘Nord can now be valued and enter development with Apmonia Therapeutics, an industrial partner of choice for enhancing cutting-edge research on the extracellular matrix."

"This new asset strengthens and diversifies Apmonia Therapeutics’ intellectual property portfolio, It provides value in this portfolio," explains Claire Verschelde, partner at ICOSA and the company’s intellectual property consultant. "With a technology platform and several proprietary assets, including the most advanced on the eve of a first clinical trial, Apmonia Therapeutics has many assets in terms of intellectual property."

On September 12, 2023 Regen Biopharma, Inc. (the "Company") reported to have entered into a securities purchase agreement (the "Purchase Agreement") with Coventry Enterprises, LLC ("Coventry"), pursuant to which Coventry Enterprises purchased a 10% unsecured promissory Note (the "Note") from the Company in the principal amount of $175,000 of which $26,250 was retained by Coventry through an Original Issue Discount (Filing, 8-K, Regen BioPharma, SEP 12, 2023, View Source [SID1234635210]).

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The Note carries "Guaranteed Interest" on the principal amount at the rate of 10% per annum for the eighteen-month term of the Note for an aggregate Guaranteed Interest $26,250. The Principal Amount and the Guaranteed Interest shall be due and payable in seven equal monthly payments of $28,750 commencing on August 12, 2024 and continuing on the 12th day of each month thereafter until paid in full not later than March 12, 2025 (the "Maturity Date").

Upon an Event of Default (as such term is defined in the Note) the Note shall become convertible, in whole or in part, into shares of Common Stock at the option of the Holder at price per share equivalent to 90% of the lowest per-share trading price for the 20 Trading Days preceding a Conversion Date.

Upon the event that while this Note has been outstanding for four months, the Company consummates another financing transaction or if the Company has an effective Regulation A Offering Statement then the Investor may choose to convert any amount up to the entire balance of the note including guaranteed interest into shares at the same offering price as the aforementioned financing transaction or the Regulation A Offering..

The foregoing description of the abovementioned Purchase Agreement and Note are not complete and are qualified in their entirety by reference to the text of the abovementioned agreements , which are attached to this Current Report on Form 8-K as Exhibit 10.1 and 10.2 and incorporated in this Item 1.01 by reference.

On September 12, 2023 the Company entered into a common stock purchase agreement (the "Equity Line Agreement") with Coventry providing for an equity financing facility (the "Equity Line"). The Equity Line Agreement provides that upon the terms and subject to the conditions in the Equity Line Agreement, Coventry is committed to purchase up to Ten Million Dollars ($10,000,000) of shares of common stock, $0.0001 par value per share (the "Common Stock"), over the 36-month term of the Equity Line Agreement (the "Total Commitment").

Under the terms of the Equity Line Agreement, Coventry will not be obligated to purchase shares of Common Stock unless and until certain conditions are met, including but not limited to a Registration Statement on Form S-1 (the "Registration Statement") becoming effective which registers Coventry’s resale of any Common Stock purchased by Coventry under the Equity Line.

From time to time over the 36-month term of the Commitment Period ( as such term is defined in the Equity Line Agreement) the Company, in its sole discretion, may provide Coventry with a draw down notice (each, a "Draw Down Notice"), to purchase a specified number of shares of Common Stock (each, a "Draw Down Amount Requested"), subject to the limitations discussed below. The actual amount of proceeds the Company will receive pursuant to each Draw Down Notice (each, a "Draw Down Amount") is to be determined by multiplying the Draw Down Amount Requested by the applicable purchase price. The purchase price of each share of Common Stock equals 80% of the lowest trading price of the Common Stock during the ten business days prior to the Draw Down Notice date (the "Pricing Period").

The maximum number of shares of Common Stock requested to be purchased pursuant to any single Draw Down Notice cannot exceed the lesser of (i) 200% of the Average Daily Traded Value ( as such term is defined in the Equity Line Agreement) during the ten business days immediately preceding the Drawdown Notice Date or (ii) $250,000. The Company is prohibited from delivering a Draw Down Notice if the sale of shares of Common Stock pursuant to the Draw Down Notice would cause the Company to issue and sell to Coventry or Coventry to acquire or purchase an aggregate number of shares of Common Stock that would result in Coventry beneficially owning more than 4.99% of the issued and outstanding shares of Common Stock of the Company.

The Company is also required to issue Coventry 125,000 shares of its Common Stock. The Common Stock will be issued in reliance upon the exemptions from the registration requirements of the Securities Act of 1933, as amended, afforded the Company under Section 4(a)(2) promulgated thereunder.

Coventry has agreed that:

(a) for so long as the market price of the Company’s common stock is above $1.25 per share and

(b) the Company is in full compliance with all agreements entered into with Coventry and

(c) and the Company has not issued any common shares at a per share price below $1.50,

Coventry will agree to a leak out provision and will not sell more than 10,000 shares of the Commitment shares without permission from the Issuer.

In connection with the Equity Line Agreement the Company also entered into a Registration Rights Agreement, dated September 12, 2023 with Coventry (the "Registration Rights Agreement"), pursuant to which the Company agreed to register for resale under the Securities Act of 1933 shares issuable in accordance with the Equity Line Agreement as well as the aforementioned 125,000 common shares issued in connection with the Equity Line Agreement in a Registration Statement to be filed with the Securities and Exchange Commission.

It is intended that, in compliance with applicable SEC Compliance and Disclosure Interpretations, the total number of common shares to be registered in the initial Registration Statement shall total no more than one-third of the company’s public float at the time of execution of the Equity Line Agreement therefore the Company shall register 1,126,954 common shares. .

The foregoing description of the abovementioned Equity Line Agreement and Registration Rights Agreement are not complete and are qualified in their entirety by reference to the text of the abovementioned agreements , which are attached to this Current Report on Form 8-K as Exhibit 10.3 and 10.4 and incorporated in this Item 1.01 by reference.

On September 12, 2023, Rocket Pharmaceuticals, Inc. (the "Company") reported to have entered into an underwriting agreement (the "Underwriting Agreement") with J.P. Morgan Securities LLC, Morgan Stanley & Co. LLC, Leerink Partners LLC and Cowen and Company, LLC, as representatives of the several underwriters named in Schedule A thereto (collectively, the "Underwriters"), pursuant to which the Company agreed to issue and sell up to (i) 7,812,500 shares of common stock (the "Shares"), and (ii) pre-funded warrants (the "Pre-Funded Warrants") to purchase 3,126,955 shares of common stock (the "Offering") (Press release, Rocket Pharmaceuticals, SEP 12, 2023, View Source [SID1234635184]). In addition, the Company granted the Underwriters a 30-day option to purchase up to an additional 1,640,918 shares of its common stock (the "Option Shares").

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The Underwriters exercised their option to purchase the Option Shares in full, and the Offering closed on September 15, 2023.

The Shares and the Option Shares were sold in the Offering at the public offering price of $16.00 per share and were purchased by the Underwriters from the Company at a price of $15.04 per share. The Pre-Funded Warrants were sold at a public offering price of $15.99 per Pre-Funded Warrant, which represents the per share public offering price for the common stock less the $0.01 per share exercise price for each such Pre-Funded Warrant. Each Pre-Funded Warrant is exercisable as of September 15, 2023 until fully exercised, subject to an ownership limitation pursuant to the Underwriting Agreement.

The Offering was made pursuant to the Company’s effective registration statement on Form S-3 (Registration No. 333-253756), which was previously filed with the Securities and Exchange Commission under the Securities Act of 1933, as amended (the "Securities Act"), and declared effective on September 10, 2021.

The net proceeds from the Offering, after (i) giving effect to the Underwriters’ full exercise of their option to purchase the Option Shares and (ii) deducting the underwriting discounts and commissions and estimated offering expenses payable by the Company, are expected to be approximately $188.9 million. The Company currently intends to use the net proceeds from the offering primarily to fund the further development of its pipeline of gene therapies for rare diseases, including the advancement of RP-A501 into a Phase 2 clinical trial and the continued clinical development of RP-A501, to accelerate the development of in-house manufacturing capabilities, and for general corporate purposes. The Company may also use a portion of the net proceeds to in-license, acquire or invest in complementary businesses or products. However, the Company currently has no agreements or commitments to complete any such transaction.

Pursuant to the Underwriting Agreement, the Company’s executive officers and directors, and certain other shareholders entered into agreements in substantially the form included as an exhibit to the Underwriting Agreement, providing for a 90-day "lock-up" period with respect to sales of the Company’s common stock, subject to certain exceptions.

The foregoing is a summary description of the Underwriting Agreement and is qualified in its entirety by the text of the Underwriting Agreement attached as Exhibit 1.1 to this Current Report on Form 8-K and incorporated herein by reference.

The form of Pre-Funded Warrant is filed as Exhibit 4.1 to this report and the description of the terms of the Pre-Funded Warrants is qualified in its entirety by reference to such exhibit.

A copy of the opinion of K&L Gates LLP relating to the validity of the Shares, the Option Shares and the Pre-Funded Warrants issued in the Offering is filed herewith as Exhibit 5.1.