Efficacy and Safety of PQ Grass in Subjects With Seasonal Allergic Rhinitis and/or Rhinoconjunctivitis Induced by Grass Pollen

Inclusion Criteria:

1. Capable of giving signed informed consent as described in Appendix 1 which includescompliance with the requirements and restrictions listed in the ICF (informedconsent form) and in this clinical trial protocol and to attend required clinicaltrial visits.

2. Subject who has a signed and dated ICF.

3. Subject must be 18 to 65 years of age inclusive, at the time of signing the ICF.

4. Male or female.

5. Female subjects who are not of childbearing potential (defined as at least 12 monthsnatural spontaneous amenorrhoea, or at least 6 weeks following surgicalmenopause/permanent sterilisation [hysterectomy, bilateral oophorectomy andbilateral salpingectomy]) or females of childbearing potential who agree to complywith the contraceptive requirements of the clinical trial protocol.

6. Good general health, as determined by the Investigator, based on a medicalevaluation, including medical history, physical examination, mental statusassessment and laboratory tests. A subject with a clinical abnormality or laboratoryparameters outside the reference range for the population being studied may beincluded only if the Investigator agrees that the finding is unlikely to introduceadditional risk factors and will not interfere with the clinical trial procedures.

7. Positive history of moderate to severe symptoms of SAR/rhinoconjunctivitis ascribedto grass (Pooideae) pollen exposure of at least 2 seasons duration, despite havingreceived allergy pharmacotherapy (e.g., antihistamines, nasal corticosteroids,leukotriene modifiers, etc.) during the last 2 consecutive grass pollen seasonsprior to the clinical trial, confirmed by subject records. Please note: Subjects with asthma may be included, but the asthma must be wellcontrolled (according to current Global Initiative for Asthma [GINA] guidelines [GINA 2022]).

8. A positive SPT (skin prick test) to histamine (wheals [longest diameter] ≥3 mm) anda negative SPT to the negative control (wheal diameter = 0 mm) at screening.

9. A positive SPT for grass pollen (wheals [longest diameter] ≥3 mm).

10. Grass specific IgE (immunoglobulin E) class ≥2 as documented by an ImmunoCAP test atscreening.

11. Forced expiratory volume in one second (FEV1) ≥70% of predicted, with a FEV1/forcedvital capacity (FVC) ratio >75% and PEFR (peak expiratory flow rate) ≥70% ofpredicted at screening.

Exclusion Criteria:

1. Pregnant or lactating subject.

2. Presence of any medical history of moderate to severe allergy symptoms (verified bya positive SPT at screening or positive specific IgE [≥2] at screening) to any otherseasonal allergen (other than grass) or perennial allergens. Exception: Period 1, Period 2 and Period 3 of the entire clinical trial will beconducted outside of the pollen season(s) of concern or perennial allergies areirrelevant due to avoidance measures (e.g., cats and dog allergy). Subjects withmild allergy symptoms (only) to any other allergen apart from grass may be includedat the discretion of the Investigator. In countries in Europe where Bermuda grass ispresent, any medical history of moderate to severe allergy symptoms to Bermuda grass (verified by a positive SPT or positive specific IgE [Class ≥2]), will alsorepresent a reason for exclusion as it will not be possible to conduct Period 1,Period 2 and Period 3 of the entire clinical trial outside of Bermuda grass pollenseason. Albeit Bermuda grass being commonly defined as a grass, it belongs to thePoaceae family, while the sentence (other than grass) in Exclusion criterion #2refers to grass of Pooideae subfamily (as defined in Inclusion criterion #7).

3. Subjects at US clinical trial sites in regions where southern grasses (Bahia grass,Bermuda grass or Johnson grass) are the dominant grasses and the main cause of grassallergy symptoms with a positive SPT to any of the 3 grasses (irrespective of theseverity of symptoms).

4. Moderate to severe symptoms during the 3 years prior to Visit 1 to any otherseasonal or perennial allergen not tested in the SPT done at screening that cannotbe avoided during the Period 1 to Period 3 of the clinical trial and the symptoms ofwhich may interfere with administration of treatment and/or impact the datacollected.

5. Presence of any medical condition that may reduce the ability to survive a seriousallergic reaction.

6. Presence of active systemic autoimmune disorder, systemic autoimmune disorders inremission or active organ specific autoimmune disorder.

7. Presence of active malignant neoplasia, severe cardiovascular disease (e.g.,coronary artery disease, cardiac insufficiency, etc.), pulmonary insufficiency,severe psychiatric disorders or primary and secondary immunodeficiencies.

8. History of any other immunological disorder or other diseases (including, but notlimited cardiovascular [including uncontrolled or inadequately controlledhypertension], gastro-intestinal, hepatic, renal, haematological, neurological,endocrine or pulmonary disease) that in the opinion of the Investigator may pose asafety risk or compromise the interpretation of efficacy of the clinical trialtreatment.

9. Presence of severe or poorly controlled or uncontrolled asthma as defined by atleast 1 of the following criteria:

10. Severe asthma (as per the current GINA guidelines [GINA, 2022]).

11. Uncontrolled or poorly controlled asthma as per the current GINA guidelines (GINA, 2022).

12. Asthma that requires more than a daily dose above 800 μg of inhaled budesonide (or clinically comparable inhaled corticosteroid) as per the current GINAguidelines (GINA, 2022).

13. History of 2 or more systemic corticosteroid courses within 6 months ofscreening or Visit 2 or 1 course of systemic corticosteroids within 3 months ofscreening or Visit 2 to treat asthma.

14. Prior intubation/mechanical ventilation for asthma.

15. Emergency room visit or hospitalisation for asthma in the 12 months prior toscreening or Visit 2.

16. Any history of a life-threatening asthma attack.

17. FEV1 <70% of predicted or FEV1/FVC ≤75% or PEFR <70% of predicted with orwithout controller medications at screening or Visit 2.

18. Presence non-atopic rhinitis and/or rhino-sinusitis (with or without polyps).

19. Presence of nasal polyps and/or chronic sinusitis.

20. Presence of any acute or chronic ocular disorder, other than allergicconjunctivitis.

21. Eye surgery within the past 6 months.

22. Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), whichmight interfere with the interpretation of the SPT results.

23. Clinical history of Type I diabetes or poorly controlled Type II diabetes.

24. Moderate to severe upper or lower respiratory infections requiring medication within 14 days before screening (Visit 1) or Visit 2.

25. Presence of acute or chronic infection, fever or inflammation at screening or Visit

27. Clinical history of severe systemic reaction or serious systemic reaction inresponse to AIT (allergen immunotherapy) in the past.

28. Clinical history of severe or life-threatening anaphylactic reactions to foods,insect venom, exercise, drugs or idiopathic anaphylaxis.

29. Clinical history of allergy, hypersensitivity or intolerance to the excipients ofthe investigational drug/placebo.

30. Clinical history of allergy, hypersensitivity or intolerance to the reliefmedications (for relief of allergy symptoms during Period 3) provided for use inthis clinical trial.

31. Clinical history of hereditary angioedema.

32. Unable to receive epinephrine therapy (i.e., use of epinephrine is contraindicatedsuch as in subjects with hyperthyroidism, uncontrolled hypertension, cardiacarrhythmias, closed angle glaucoma or subjects taking other sympathomimetics).

33. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.

34. Clinical history of drug or alcohol abuse, which, in the Investigator's opinion,could interfere with the subject's ability to participate in the clinical trial.

35. Subjects who have suspicion or symptoms of severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection (as assessed by the Investigator) or who havehad unprotected contact with a confirmed case of COVID-19 (coronavirus disease 2019)in the 2 weeks prior to screening or Visit 2 (based on the Investigator'sdiscretion).

36. Subjects who were hospitalised for COVID-19 within 6 months prior to screening orVisit 2.

37. Any history of AIT for grass pollen allergy in the past or history of AIT for anyother type of allergy (excluding food allergy) in the past 5 years.

38. Inability to adhere to the washout periods listed in the protocol, with respect toscreening and to refrain from using the medications indicated until after Visit 11.

39. Treatment with a preparation containing MPL (monophosphoryl lipid-A) (e.g.,Cervarix, Shingrix, Fendrix) within 2 years prior to Visit 1 and until aftercompletion of Visit 11 (with the exception of the investigational drug).

40. Previous history of epinephrine auto-injector use.

41. β-blocker medication (local or systemic, including eye drops) for any indication.

42. Monoamine oxidase inhibitors and tricyclic antidepressants. Please note: Tricyclicantidepressants should be avoided at least 2 weeks prior to screening.

43. Any previous therapy (within the previous 5 years) or current therapy with anti IgE (e.g., omalizumab [Xolair]) or anti-interleukins (e.g., mepolizumab).

44. Current or past therapy (within the previous 5 years) with any otherimmunomodulatory biologics.

45. Unable to refrain from any vaccination (including influenza vaccine and COVID-19vaccine) during the clinical trial (unless administered >30 days prior torandomisation). Please note: Emergency vaccinations (e.g., tetanus due to injury) can beadministered at any time. Booster vaccinations (only) for COVID-19 can beadministered during the clinical trial apart from during the treatment period. Thereshould be at least 14 days interval from the last administration of theinvestigational drug/placebo prior to administration of a COVID-19 boosterinjection.

46. Participation in a clinical research trial with any investigational drug within 4weeks of Visit 1 or concomitantly with this clinical trial. Please note: The period of exclusion begins at the time of the last visit of theprior clinical research trial. Subjects consented and screened, but not dosed in theprior clinical research trial are not excluded.

47. Personal, financial or other dependent relationship (e.g., employee or immediaterelative) with the clinical trial site, Sponsor, Sponsor's representative, oranother individual who has access to the clinical trial protocol.

48. Vulnerable subjects or those in judicial or governmental detention, detainment orimprisonment in a public institution.

49. Subjects likely to have prolonged periods of absence (e.g., business or personaltravel) during the GPS defined as:

• Absence of a total of 22 days or more in similar geographical regions (asdetermined by the Investigator), with no single trip in a similar geographicalregion exceeding 14 days.

• Absence of a total of 15 days or more in non-similar geographic regions (asdetermined by the Investigator), with no single trip in a non-similargeographical region exceeding 7 days.

41. Have changed residence to a different geographical region(s) since the last GPS.

Exception: The old and new residences are in the same or similar geographical region as determined by the Investigator.