During the financial year a total of £52m (2017: £41m) was deployed into the portfolio, including three new and nine existing portfolio companies. Arix continues to balance risk by deploying small amounts (approximately 4% of gross portfolio capital) into very early stage seed ventures (discovery portfolio), with 96% of portfolio capital deployed in later stage ventures – either clinically or pre-clinically validated companies (core portfolio).
Highlighted below are some of the notable investments that were made in the financial year. These include new investments into existing portfolio companies (not including previously tranched capital) and investments into new portfolio companies
New core portfolio companies
- VelosBio: £5.1m invested in Series A fundraise, Tranche 1 (£8.4m committed in total)
- Pharmaxis: £8m VIPE investment
- New SeedCo: £2.4m investment
Existing portfolio companies
- Autolus: £5.5m invested in the IPO
- Artios: £5.8m invested (£1.5m Series A tranche 3, £3.7m Series B tranche 1, £0.6m from an existing shareholder)
- Harpoon: £6.1m invested in the Series C fundraise
- LogicBio: £5.4m invested in the IPO
- Iterum: £3.3m invested in the IPO, £0.3m invested in the market
Post year-end investments
A further £15.9m has been committed or invested post year-end, into Harpoon Therapeutics and Imara, a new portfolio company
- Harpoon: £4.6m invested in the IPO
- Imara: £11.3m committed in the Series A fundraise
In 2018 we expanded our investment team, with the appointment of Christian Schetter as Entrepreneur-in-Residence. Christian has over 20 years industry experience across the life sciences sector, and joins Arix from German immuno-oncology company Rigontec GmbH, where he was CEO for four years before its acquisition by Merk & Co. He has a track record of creating companies that foster exciting science and securing impressive exits and his extensive experience of building companies in the life science industry will greatly benefit Arix as we continue to build on our existing investments and leverage our extensive pipeline.
- Significant period of clinical progress with encouraging data from AUTO1 and AUTO3 programmes
- Dosed first patient in AUTO4 and pre-clinical data read-outs for AUTO5
- Successful IPO on NASDAQ, raising $172m
Autolus made significant progress in 2018 and notably completed an oversubscribed IPO on NASDAQ, raising $172.2m. Arix invested a further £5.5m in the IPO, retaining a 7.9% stake, which was valued at £81.5m at 31 December, a £55.9m increase in value over the last 12 months.
The company reported positive initial Phase 1 data from its AUTO3 programme in Diffuse Large B-cell lymphoma (DLBCL) and paediatric Acute Lymphoblastic Leukaemia (pALL). Early efficacy data is encouraging, with notable dose responses and manageable safety data. Autolus also announced that it had dosed its first patient in the Phase 1/2 trial of AUTO4 in TRBC1-positive peripheral T-cell lymphoma and reported encouraging pre-clinical data from its sister programme, AUTO5 targeting TRBC2-positive lymphoma. Additionally, Autolus licensed two new clinical stage programmes: AUTO1 in paediatric ALL and adult ALL (UCL) and the AUTO6 programme in Neuroblastoma (in partnership with Cancer Research UK.)
Post year end, Autolus presented interim results from the ongoing Phase 1 CARPALL trial (Pediatric Acute Lymphoblastic Leukaemia) of AUTO1. Updated AUTO1 data showed comparable to better persistence and survival of patients comparable to Kymriah, all with a better safety profile. This is despite the fact that the study included patients post CD19 and CD22 targeted therapies, which were excluded from the Kymriah trial. Data is supportive for the company's activities in adult patients with first update scheduled for April 2019. The company expects to see full Phase 1 data from AUTO1, AUTO2 and AUTO3 programmes by the end of 2019, with initial AUTO4 data in H2. (See case study for more details.)
- Positive Phase 1b/2 data
- Phase 3 ready
Aura released positive data from the its Phase 1b/2 study with light-activated AU-011 in 2018. The study has shown that the drug was well tolerated, with clear evidence of tumour control and preservation of visual acuity at long term follow-up. This data provides the evidence that AU-011 can be a minimally invasive, in-office procedure with no radiation for early intervention of small lesions and tumours.
Post year end Aura announced that it has received written confirmation from the U.S. Food and Drug Administration (FDA) regarding agreement on the design of its Phase 3 trial; the result of a successful 'End of Phase 2' meeting with the FDA. In addition to the design of the Phase 3 trials, the FDA agreed with Aura's proposed safety database. The FDA also agreed that no further non-clinical studies are needed.
Read more about Aura
- Dosed first patient in HPN424 Prostate Cancer Trial
- Successful Series C at 68% uplift to Series B price
- $81m IPO on NASDAQ post year end
Harpoon met a significant milestone this year, with the first patient dosed in its HPN424 prostate cancer trial. In November 2018, Harpoon completed a $70m Series C investment round at a 68% uplift to the Series B price resulting in a notable uplift to our holding. Arix invested $8m (£6.1m) in the round to retain an 11.3% stake.
In December 2018, Harpoon announced that it had filed for a proposed initial public offering in the United States, a process that completed post year end. The company listed on NASDAQ in February 2019, raising total proceeds of $81m. Arix invested a further $6m (£4.6m) in the IPO to retain a stake of 12.1% in Harpoon, which was valued at £31.3m at the IPO price of $14 (at the close of business on 13 February 2019). This represents a gain of £12.1m on total cash invested in Harpoon by Arix. At year-end, Arix's pre-IPO stake in Harpoon was valued at £23.9m.
Proceeds from the Series C and IPO will be used to advance Harpoon's pre clinical and clinical trials. The company plans to initiate further Phase 1 clinical trials for HPN536 (a mesothelin- targeting TriTAC) for the treatment of mesothelin-expressing tumours, and HPN217 (a BCMA-targeting TriTAC) for the treatment of multiple myeloma in 2019. We also expect to see initial Phase 1 data from HPN424 this year.
- IPO on NASDAQ, raising $81m
- Initiated three pivotal Phase 3 trials
Iterum made significant progress during the year, notably initiating three Phase 3 pivotal trials in uncomplicated urinary tract infections (uUTI), complicated urinary tract infections (cUTI) and complicated intra-abdominal infection (cIAIs). Iterum's lead product candidate sulopenem's is potentially the first penem drug that is available as an oral drug. (To date these drugs have only been via IV, limiting their use to hospital setting.) Sulopenem's clear commercial pathway is supported by rising resistance rates to existing treatment options and its ability to provide significant cost-saving advantages for hospitals, by allowing earlier patient discharge by switching from IV to oral treatment. There is also a significant opportunity for oral sulopenem in the community setting, where rising rates of resistance, safety concerns with fluoroquinolones, and a lack of new treatment options make sulopenem an attractive treatment for elevated risk patients with urinary tract infections. Iterum expects Phase 3 data from all three trials (uUTI, cUTI and cIAI) in 2H2019 and expects to file its new drug applications (NDAs) with the FDA by the end of 2019.
Furthermore, Iterum was the first Arix portfolio company to IPO, raising total proceeds of $81m. Since the IPO in May, Iterum shares have suffered due to a weak anti-infectives backdrop but our fundamental belief in the company has not changed. Despite the struggles of the public market comps, we strongly believe that Iterum is a commercially differentiated asset that has much potential.
- Initiated Phase 2 AKI trial
- Completed enrollment of Phase 3 NSTI trial
During 2018 Atox continued to make good operational progress, notably initiating the Phase 2 REAKT (Reltecimod Efficacy for Acute Kidney Injury Trial) study.
Reltecimod, Atox Bio's lead product, is initially being developed to treat Necrotizing Soft Tissue Infections (NSTI), a rare, life-threatening infection with high morbidity and mortality. The Phase 3 trial, also known as the ACCUTE trial (Reltecimod Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections), is designed as a single pivotal study to assess the efficacy and safety of Reltecimod versus placebo in patients with NSTI. Previously, Reltecimod completed a phase 2 study in NSTI. Results demonstrated that patients treated with Reltecimod had a meaningful improvement across multiple end points. In a subset of patients from the phase 2 NSTI study, characterised as suffering from AKI as part of the disease process, initial data suggest that Reltecimod provides a treatment benefit (improved renal function and recovery from AKI).
Data from the Phase 3 NSTI trial is expected by the end of 2019.
- Initiated Phase 2 APX001 trial
- Phase 2 data in 2019
Amplyx Pharmaceuticals is developing a new class of antifungal medicine to overcome the limitations of existing therapeutic options. Amplyx's lead programme APX001 is a broad-spectrum antifungal drug with a novel mechanism of action for the treatment of life-threatening, invasive fungal infections caused by Candida. There has not been a new class of antifungal drug approved since 2001, and many existing antifungal agents are difficult to use, poorly tolerated or ineffective due to the rise of drug-resistant strains.
In November 2018 Amplyx dosed the first patient in its Phase 2 clinical programme to evaluate the efficacy and safety of APX001 in the treatment of infections caused by Candida. This trial will aim to validate robust preclinical and Phase 1 data and demonstrate clinical proof-of-concept for APX001 as a novel treatment for patients with difficult-to-treat and often deadly Candida infections. Initial results are expected by the end of 2019.
- Good clinical progress in 2018; positive Phase 2 COPD data readouts and new trial initiations
Verona Pharma plc is an LSE and NASDAQ-listed clinical stage biopharmaceutical company focused on the development of ensifentrine (RPL554), a dual inhibitor of enzymes phosphodiesterase 3 and phosphodiesterase 4 (PDE3/4 inhibitor). This is an inhaled novel compound that aims to provide both bronchodilation (PDE3) and anti-inflammatory (PDE4) effects in a single molecule - it will be the first dual action product and the first new class of bronchodilator for many years. The aim is to treat respiratory diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) where there is a need for incremental lung function improvement.
The company continued to make solid clinical progress in 2018 for maintenance treatment of COPD, with the nebulizer formulation achieving positive top-line data in a four-week Phase 2b placebo-controlled clinical trial in 403 patients. Reporting initial results in March, ensifentrine met the primary endpoint at all doses (P<0.001), showing a clinically meaningful and statistically significant bronchodilator effect after four weeks of dosing and encouraging performance on other measures of the disease.
Post year end, Verona reported mixed top line data from its 79-patient Phase 2a COPD trial evaluating nebulized ensifentrine treatment over three days on top of dual therapy of a long-acting muscarinic antagonist (LAMA) and a long-acting βeta2-agonist (LABA). With a challenging trial design that promoted a large response to underlying standard of care of LAMA plus LABA, ensifentrine added some further lung function improvement, but the effect for the primary endpoint was not statistically significant. The stock market took this lack of statistical significance as a negative. However, the combination of all 13 clinical studies completed to date, including this equivocal Phase 2, has prepared the way for a six-month Phase 2b study due to start in 2019 that will set the programme up for a pair of pivotal Phase 3 trials. The company is positioning ensifentrine as an add-on to first line therapy in COPD, which is generally a LAMA.
Advanced Dry Powder Inhaler (DPI) and Metered Dose Inhaler formulations of ensifentrine are also in development, with the potential to reach a substantially larger number of COPD patients than via nebulizer administration. The first DPI clinical trial in COPD patients was initiated in December 2018; initial results expected in the first quarter of 2019. The company calculates the market for nebulised therapy on top of LAMA alone or dual LAMA/LABA to be 280,000 patients in the USA; the DPI/MDI inhaler market in moderate-to-severe COPD is 1.72million people in the US.
In March 2018 Verona also released positive top-line data from a small, ten patient Phase 2a clinical trial in Cystic Fibrosis (CF). Development in CF will build upon the upcoming COPD Phase 2b.
- Positive Phase 1 LOXL2 data
- Initiated Phase 1 LOX-oral (cancer) trial
Pharmaxis is a research and development company working on new therapies to treat inflammatory and fibrotic diseases such as NASH, pulmonary fibrosis, kidney and liver fibrosis, inflammatory bowel diseases and cancer.
In 2018 Pharmaxis consolidated its position as a significant competitor in the NASH market as the Company's LOXL2 inhibitor completed phase 1 studies, demonstrating a best in class profile for two compounds. Positive Phase 1 clinical trial results were reported on both compounds, confirming long lasting inhibition of the target LOXL2 enzyme. In January 2019 Pharmaxis announced that, following completion of 13 week toxicity studies, the programme was ready to enter phase 2 clinical studies for diseases such as NASH, IPF and cardiac fibrosis.
In addition, Pharmaxis announced the dosing of the first patient in Boehringer Ingelheim's Phase 2a clinical trial in patients with diabetic retinopathy (DR), triggering a €10 million (~A$15million) milestone payment to Pharmaxis. DR is the second disease to be targeted with the drug known as BI 1467335 which was discovered by Pharmaxis.
Post year end, Pharmaxis made further clinical progress, launching a Phase 1 clinical trial of a new compound targeting pancreatic cancer. Dosing of the first subjects has begun, trialling an anti-fibrotic Lysyl Oxidase (LOX) inhibitor which has delivered positive results in pre-clinical testing. The compound is an oral once-a-day drug that inhibits all lysyl oxidase family members (LOX, LOXL1, 2, 3 & 4). It has shown significant reductions in fibrosis in in-vivo models of kidney fibrosis, lung fibrosis, myelofibrosis and pancreatic cancer. It is potentially suited to the treatment of severe fibrosis as well as cancer with prominent stroma (connective tissue) or fibrotic metastatic niches.
- Expands breadth of portfolio with investment in sickle cell disease via a later-stage clinical asset in phase 2
- Phase 2 data in 2019
Post year end, we co-led the $63m Series B for Imara; we committed to invest $15.0 million (£11.3m) for a 10% stake on a fully diluted basis.
Imara is a company dedicated to developing novel therapeutics for chronic treatment of Sickle Cell Disease ('SCD') and other hemoglobinopathies. Imara's lead programme, IMR-687, is designed to be a disease-modifying therapy that acts on both red and white blood cells with the potential to help healthcare providers create better treatment outcomes for patients. Its profile is attractive as it has a dual mechanism of action on red and white blood cells, once daily dosing, very clean safety profile, and potential impact on fetal hemoglobin.
Imara adds a new therapeutic area and expands the breadth of our portfolio into non-oncology haematology and also adds another later-stage clinical asset to the portfolio. Imara's lead programme, IMR-687, is at an exciting point in clinical development and is currently being evaluated in a Phase 2a study in sickle cell patients. We expect to see Phase 2a data soon; initial data in 2H 2019 and full data in Q1 2020.
- Oversubscribed Series B attracting interest from big pharma
- Arix became the largest shareholder following the Series B
Artios a leading DNA Damage Response (DDR) company developing innovative treatments for cancer. The company closed an oversubscribed $84m Series B in August in a round pulled together by Arix, co-led by Andera Partners (Paris) and LSP (Amsterdam). New investors included Novartis and Pfizer venture funds.
As part of the Financing, Arix, committed to invest £8m over two tranches; completed its remaining £1.5m Series A commitment and invested a further £0.6m by purchasing a stake from an existing shareholder. Following this investment, Arix became the largest shareholder in Artios, retaining a 12.4% stake on a fully diluted basis.
The financing recognised a 26% uplift in the book value of Arix's Series A investment in Artios. Arix's total interest in Artios, including current commitments, has risen to £15.3m, from £5.1m at December 2017.
Artios is now funded through five proof of concept studies – three for lead asset Polymerase Theta, and two for additional assets. The company has four first-in-class, highly differentiated assets in pipeline and a leading position on Pol Theta – the hottest target after PARP in DDR. We expect to select clinical candidates in the first half of 2019 and to start clinical testing in 2020
- Successful NASDAQ IPO, raising $80m
- Clinical trials commencing in 2019
LogicBio Therapeutics is a genome editing company focused on developing medicines to durably treat rare diseases in patients with significant unmet medical needs using GeneRide™, its proprietary technology platform.
Logic completed a key milestone in 2018 following its successful NASDAQ IPO in October. The company raised gross proceeds of $80 million and is now well positioned to develop ground-breaking solutions for patients with severe genetic diseases. Arix retains a stake of 12.9% in LogicBio following the IPO; at year-end the total value of Arix's shareholding in LogicBio is £24.3m, a £14.1m increase on total cash invested by Arix. We expect Phase 1 clinical trials to commence in Q4 2019.
- Co-investment with pharmaceutical partner Takeda
- Experienced team with a track record in generating value
- Phase 1 trial initiated in 2019
VelosBio, is a next-generation oncology company, developing novel antibody-drug conjugates (ADCs) to treat haematological cancers and solid tumours. ADCs are highly potent drugs designed as a targeted therapy for the treatment of people with cancer. In contrast to traditional chemotherapeutic drugs, ADCs only target cancer cells so that healthy cells are less affected. Velos was founded by the former Acerta team, which developed the approved blood cancer treatment, CALQUENCE (acalabrutinib), acquired by AstraZeneca for up to $7bn in 2015. This is a team with extensive experience in M&A, navigating clinical pathways and mitigating risk to get a drug to market.
Velos is a new portfolio company for 2018; we co-led the Series A with Sofinnova Ventures, investing $11m (£8.4m) for an 11.2% stake. Importantly this is a company sourced through our pharmaceutical partner Takeda, illustrating the importance of these partnerships, as not only potential acquirers and partners of our companies, but also as a further source of investment opportunities.
This investment broadens our oncology portfolio adding ADCs alongside a range of different therapeutic modalities including CAR-T, DNA damage response / synthetic lethality, bi-specific antibodies, and targeted viruses (Harpoon, Aura, Autolus, Artios).
Our discovery portfolio contains our earliest stage companies: Depixus, Mitoconix, PreciThera, OptiKira and a new seed company sourced through our relationship with The Max Planck Lead Discovery Center. These investments collectively are valued at £6.2m, accounting for 3.5% of gross portfolio value.
These investments offer exciting opportunities, but also carry higher risk. We invest small amounts at this stage, until milestones are met. We take a conservative approach to valuation, with a focus on preserving shareholder capital. To this end, OptiKira was written down by £0.3 million in the period to reflect slower than expected progress on delivering pre-clinical proof-of-concept and a pharmaceutical lead candidate. We have not reached the level of conviction in Mitoconix's lead programme necessary to justify maintaining its current valuation in our portfolio; as result our holding was written down by £0.6 million in 2018.
There remains cause for optimism about the portfolio more broadly, notably Depixus, which raised significant non dilutive funding in 2018 and is well poised for its next stage of development. In addition, we co-founded our first company, based on novel discoveries in the innate immune system emerging from the Max Planck Lead Discovery Center.
Outlook & catalysts
The year ahead will be important for a number of our portfolio companies as they reach significant clinical and development milestones during the year. We also continue to see a strong pipeline of opportunities through our global networks and partnerships, and expect to invest in new and existing portfolio companies over the course of the year. New investments will continue to be guided by the quality of the science, the commercial opportunity and, importantly, the potential benefits for patients.
Over the next 12 months, we expect to see 19 data readouts across the core portfolio, including four pivotal Phase 3 trials. Additionally we expect a further eight new trials to initiate within the next 12 months, including first clinical trials from LogicBio.
Catalysts expected in 2019:
- Harpoon: HPN424 (Prostate Cancer)
- Autolus: AUTO1 (Adult ALL)
- Autolus: AUTO1 (Pediatric ALL)
- Autolus: AUTO2 (Multiple Myeloma)
- Autolus : AUTO 3 (Adult DLBCL)
- Autolus : AUTO 3 (Pediatric ALL)
- Autolus: AUTO4 (T Cell Lymphoma)
- Pharmaxis: Lox-oral (Cancer)
- Amplyx : APX001 (Invasive fungal infections)
- Aura: AU-011 (Ocular melanoma) – additional update
- Verona: RPL554 COPD (DPI)
- Verona: RPL554 COPD (MDI)
- Verona: RPL554 COPD (as add onto LAMA+LABA)
- Pharmaxis SSAO (NASH)
- Imara: IMR-687 (Sickle Cell Disease)
- AtoxBio- ACCUTE (Necrotising Soft Tissue Infections)
- Iterum - SURE 3 (Complicated Intra-Abdominal Infections)
- Iterum - SURE 2 (Complicated Urinary Tract Infections)
- Iterum - SURE 1 (Uncomplicated Urinary Tract Infections)
- Autolus: AUTO5 (Peripheral TCL)
- Harpoon: HPN536 (MSLN/ Ovarian Cancer and other solid tumours)
- Harpoon: HPN127 (Multiple Myeloma)
- Logic Bio: Methylmalonic acidemia (MMA)
- Pharmaxis : LOX (oral) – myelofibrosis
- Pharmaxis: LOX (oral) for pancreatic cancer
- Verona RPL1554 COPD (MDI)
Autolus data could result in up to three Phase 2-3 trials commencing in H2 2019